Anti-ITGA3 antibodies, activatable anti-ITGA3 antibodies, and methods of use thereof
First Claim
Patent Images
1. An isolated 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, wherein the AB comprises a VH CDR1 comprising the amino acid sequence EYIIH (SEQ ID NO:
- 13);
a VH CDR2 comprising the amino acid sequence 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), and wherein the AB is humanized.
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Accused Products
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.
33 Citations
48 Claims
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1. An isolated 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, wherein the AB comprises a VH CDR1 comprising the amino acid sequence EYIIH (SEQ ID NO:
- 13);
a VH CDR2 comprising the amino acid sequence 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), and wherein the AB is humanized. - View Dependent Claims (2, 3)
- 13);
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4. An activatable antibody that, in an activated state, binds ITGa3 comprising:
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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, wherein the AB comprises a VH CDR1 comprising the amino acid sequence EYIIH (SEQ ID NO;
13);
a VH CDR2 comprising the amino acid sequence 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), and wherein the AB is humanized;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; and 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 (5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 25, 41, 42, 43, 44, 45, 46, 47, 48)
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18. An activatable antibody comprising an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian ITGa3, a masking moiety (MM), and a cleavable moiety (CM), wherein the activatable antibody has one or more of the following characteristics selected from the group consisting of:
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(i) the activatable antibody comprises a heavy chain comprising an amino acid sequence of SEQ ID NO;
320; and
a light chain sequence 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;(ii) the AB comprises a VH CDR1 comprising the amino acid sequence EYIIH (SEQ ID NO;
13);
a VH CDR2 comprising the amino acid sequence 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);(iii) the AB comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
4-6 and 8-10, and a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
11 and 12; and(iv) the AB comprises a VH CDR1 comprising the amino acid sequence EYIIH (SEQ ID NO;
13);
a VH CDR2 comprising the amino acid sequence 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), the MM comprises an amino acid sequence selected from the group consisting of SEQ ID NOs;
22-54, and the CM comprises an amino acid sequence selected from the group consisting of SEQ ID NOs;
182-249 and 276-316.
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26. A conjugated activatable antibody that, in an activated state, binds ITGa3 comprising:
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(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, wherein the AB comprises a VH CDR1 comprising the amino acid sequence EYIIH (SEQ ID NO;
13);
a VH CDR2 comprising the amino acid sequence 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), and wherein the AB is humanized;(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; 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 (27, 28, 29, 30, 31, 32, 33, 34)
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35. A conjugated antibody comprising:
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(a) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian ITGa3, wherein the AB comprises; (i) a VH CDR1 comprising the amino acid sequence EYIIH (SEQ ID NO;
13);
a VH CDR2 comprising the amino acid sequence 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;
4-6 and 8-10, and a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
11 and 12;
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 NO;
322; and(b) an agent conjugated to the AB, wherein 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.
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36. A conjugated activatable antibody that, in an activated state, binds to ITGa3, 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 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;
4-6 and 8-10, 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 (37, 38, 39, 40)
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Specification