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US 2016/0355587 A1Published application
Anti-cd166 antibodies, activatable anti-cd166 antibodies, and methods of use thereof
AssigneeCytomX Therapeutics, Inc.
InventorsJames William West, Jason Gary Sagert, Jonathan Alexander Terrett, Annie Yang Weaver, Luc Roland Desnoyers, Shweta Singh
Life of this patent
Estimating the term…
Abstract
The invention relates generally to antibodies that bind CD166, activatable antibodies that specifically bind to CD166 and methods of making and using these anti-CD166 antibodies and anti-CD166 activatable antibodies in a variety of therapeutic, diagnostic and prophylactic indications.
Claims87
An isolated antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB specifically binds human CD166 and cynomolgus monkey CD166.
An activatable antibody that, in an activated state, binds CD166 comprising:
- an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB specifically binds human CD166 and cynomolgus monkey CD166;
- a masking moiety (MM) coupled to the AB that inhibits the binding of the AB to CD166 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.
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An activatable antibody comprising an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, a MM, and a CM, wherein the activatable antibody has one or more of the following characteristics selected from the group consisting of:
- (i) the activatable antibody comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:
- 239;
- and a light chain sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 240, 242, 244, 246, 248, 303, 310, 312, 314, 316, 371, 372, 375, 376, 379, 380, 383, 384, 387, 388, 391, 392, 395, 396, 399, 400, 403, 404, 407, 408, 411, 412, 415, 416, 419, 420, 423, 424, 427, 428, 431, 432, 435, 436, 439, 440, 443, 444, 447, 448, 451, 452, 455, 456, 459, 460, 463, 464, 467, 468, 471, and 472;
- (ii) the MM comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 135-238, and the CM comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 18-87 and 318-358;
- (iii) the AB comprises the VH CDR1 amino acid sequence GFSLSTYGMGVG (SEQ ID NO:
- 127);
- the VH CDR2 amino acid sequence NIWWSEDKH (SEQ ID NO:
- 128);
- the VH CDR3 amino acid sequence IDYGNDYAFTY (SEQ ID NO:
- 129);
- the VL CDR1 amino acid sequence RSSKSLLHSNGITYLY (SEQ ID NO:
- 130) or RSSQSLLHSNGITYLY (SEQ ID NO:
- 131);
- the VL CDR2 amino acid sequence QMSNLAS (SEQ ID NO:
- 132) or QMSNRAS (SEQ ID NO:
- 133);
- and the VL CDR3 amino acid sequence AQNLELPYT (SEQ ID NO:
- 134);
- (iv) the activatable antibody comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 121 and 122, and a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 123-126, 363-370, 373, 374, 377, 378, 381, 382, 385, 386, 389, 390, 393, 394, 397, 398, 401, 402, 405, 406, 409, 410, 413, 414, 417, 418, 421, 422, 425, 426, 429, 430, 433, 434, 437, 438, 441, 442, 445, 446, 449, 450, 453, 454, 457, 458, 461, 462, 465, 466, 469, 470, 473, and 474;
- and
- (v) the AB comprises the VH CDR1 amino acid sequence GFSLSTYGMGVG (SEQ ID NO:
- 127);
- the VH CDR2 amino acid sequence NIWWSEDKH (SEQ ID NO:
- 128);
- the VH CDR3 amino acid sequence IDYGNDYAFTY (SEQ ID NO:
- 129);
- the VL CDR1 amino acid sequence RSSKSLLHSNGITYLY (SEQ ID NO:
- 130) or RSSQSLLHSNGITYLY (SEQ ID NO:
- 131);
- the VL CDR2 amino acid sequence QMSNLAS (SEQ ID NO:
- 132) or QMSNRAS (SEQ ID NO:
- 133);
- and the VL CDR3 amino acid sequence AQNLELPYT (SEQ ID NO:
- 134), the MM comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 135-238, and the CM comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 18-87 and 318-358.
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A conjugated activatable antibody that, in an activated state, specifically binds to mammalian CD166 comprising:
- (a) an activatable antibody comprising:
- (i) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB specifically binds human CD166 and cynomolgus monkey CD166;
- (ii) a masking moiety (MM) coupled to the AB that inhibits the binding of the AB to CD166 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.
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A conjugated antibody comprising:
- (a) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB comprises:
- (i) the VH CDR1 amino acid sequence GFSLSTYGMGVG (SEQ ID NO:
- 127);
- the VH CDR2 amino acid sequence NIWWSEDKH (SEQ ID NO:
- 128);
- the VH CDR3 amino acid sequence IDYGNDYAFTY (SEQ ID NO:
- 129);
- the VL CDR1 amino acid sequence RSSKSLLHSNGITYLY (SEQ ID NO:
- 130) or RSSQSLLHSNGITYLY (SEQ ID NO:
- 131);
- the VL CDR2 amino acid sequence QMSNLAS (SEQ ID NO:
- 132) or QMSNRAS (SEQ ID NO:
- 133);
- and the VL CDR3 amino acid sequence AQNLELPYT (SEQ ID NO:
- 134), or
- (ii) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 121 and 122, and a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 123-126, 363-370, 373, 374, 377, 378, 381, 382, 385, 386, 389, 390, 393, 394, 397, 398, 401, 402, 405, 406, 409, 410, 413, 414, 417, 418, 421, 422, 425, 426, 429, 430, 433, 434, 437, 438, 441, 442, 445, 446, 449, 450, 453, 454, 457, 458, 461, 462, 465, 466, 469, 470, 473, and 474, or
- (iii) a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
- 239;
- and a light chain sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 240, 242, 244, 246, 248, 303, 310, 312, 314, 316, 371, 372, 375, 376, 379, 380, 383, 384, 387, 388, 391, 392, 395, 396, 399, 400, 403, 404, 407, 408, 411, 412, 415, 416, 419, 420, 423, 424, 427, 428, 431, 432, 435, 436, 439, 440, 443, 444, 447, 448, 451, 452, 455, 456, 459, 460, 463, 464, 467, 468, 471, and 472;
- 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.
21 more elements
A conjugated activatable antibody that, in an activated state, binds to CD166, comprising:
- (a) an activatable antibody comprising:
- (i) an antibody or an antigen binding fragment thereof (AB) that specifically binds to mammalian CD166, wherein the AB specifically binds human CD166 and cynomolgus monkey CD166;
- (ii) a masking moiety (MM) coupled to the AB that inhibits the binding of the AB to CD166 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) the VH CDR1 amino acid sequence GFSLSTYGMGVG (SEQ ID NO:
- 127);
- the VH CDR2 amino acid sequence NIWWSEDKH (SEQ ID NO:
- 128);
- the VH CDR3 amino acid sequence IDYGNDYAFTY (SEQ ID NO:
- 129);
- the VL CDR1 amino acid sequence RSSKSLLHSNGITYLY (SEQ ID NO:
- 130) or RSSQSLLHSNGITYLY (SEQ ID NO:
- 131);
- the VL CDR2 amino acid sequence QMSNLAS (SEQ ID NO:
- 132) or QMSNRAS (SEQ ID NO:
- 133);
- and the VL CDR3 amino acid sequence AQNLELPYT (SEQ ID NO:
- 134), or
- (ii) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 121 and 122, and a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 123-126, 363-370, 373, 374, 377, 378, 381, 382, 385, 386, 389, 390, 393, 394, 397, 398, 401, 402, 405, 406, 409, 410, 413, 414, 417, 418, 421, 422, 425, 426, 429, 430, 433, 434, 437, 438, 441, 442, 445, 446, 449, 450, 453, 454, 457, 458, 461, 462, 465, 466, 469, 470, 473, and 474, or
- (iii) a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:
- 121, 122, and 239, and a light chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO:
- 239;
- and a light chain sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 240, 242, 244, 246, 248, 303, 310, 312, 314, 316, 371, 372, 375, 376, 379, 380, 383, 384, 387, 388, 391, 392, 395, 396, 399, 400, 403, 404, 407, 408, 411, 412, 415, 416, 419, 420, 423, 424, 427, 428, 431, 432, 435, 436, 439, 440, 443, 444, 447, 448, 451, 452, 455, 456, 459, 460, 463, 464, 467, 468, 471, and 472;
- and
- 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.
28 more elements
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A conjugated activatable antibody or conjugated antibody comprising:
- an antibody or antigen binding fragment thereof (AB) that, in an activated state, binds CD166;
- and
- a toxin conjugated to the AB via a linker,
- wherein the conjugated activatable antibody or the conjugated antibody comprises amino acid sequences, a linker, and a toxin selected from a single row in Table C, wherein for the given combination:
- (a) the AB comprises a heavy chain comprising the amino acid sequence of the heavy chain sequence or heavy chain variable domain sequence corresponding to the given combination in the single row listed in Table C,
- (b) the AB comprises a light chain comprising the amino acid sequence of the light chain sequence or light chain variable domain sequence corresponding to the given combination in the single row listed in Table C, and
- (c) the linker and the toxin comprise the linker and the toxin corresponding to the given combination in the single row listed in Table C.
4 more elements
Dependencies are inferred from the claim text.