Back to results
US 12,721,901 B2Granted
Antigen-binding protein constructs and uses thereof
AssigneeMythic Therapeutics, Inc.
InventorsAlexander J. Nichols, Brian P. Fiske, Nimish Gera
Life of this patent
Estimating the term…
Abstract
Provided herein are antigen-binding protein constructs and uses of the same.
Claims21
A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising:
- a first antigen-binding domain that is capable of specifically binding CD123 or an epitope of CD123 presented on the surface of a target mammalian cell,
- wherein the first antigen-binding domain comprises:
- a heavy chain variable domain of SEQ ID NO:
- 1 and a light chain variable domain of SEQ ID NO:
- 64, SEQ ID NO:
- 70, SEQ ID NO:
- 74, SEQ ID NO:
- 77, SEQ ID NO:
- 78, or SEQ ID NO:
- 79;
- or
- a heavy chain variable domain of SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 20, SEQ ID NO:
- 22, SEQ ID NO:
- 26, SEQ ID NO:
- 40, SEQ ID NO:
- 46, SEQ ID NO:
- 47, SEQ ID NO:
- 48, SEQ ID NO:
- 49, SEQ ID NO:
- 50, SEQ ID NO:
- 51, SEQ ID NO:
- 52, SEQ ID NO:
- 81, SEQ ID NO:
- 82, SEQ ID NO:
- 83, SEQ ID NO:
- 84, SEQ ID NO:
- 85, SEQ ID NO:
- 86, SEQ ID NO:
- 87, SEQ ID NO:
- 88, SEQ ID NO:
- 89, SEQ ID NO:
- 90, SEQ ID NO:
- 91, SEQ ID NO:
- 92, SEQ ID NO:
- 93, SEQ ID NO:
- 94, SEQ ID NO:
- 95, SEQ ID NO:
- 96, SEQ ID NO:
- 97, SEQ ID NO:
- 98, SEQ ID NO:
- 99, or SEQ ID NO:
- 100 and a light chain variable domain of SEQ ID NO:
- 2;
- and wherein:
- (i) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0;
- or
- (ii) the dissociation constant (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the Kp at a pH of about 7.0 to about 8.0.
49 more elements
A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising:
- a first antigen-binding domain that is capable of specifically binding CD123 or an epitope of CD123 presented on the surface of a target mammalian cell;
- and
- a conjugated toxin, radioisotope, drug, or small molecule,
- wherein the first antigen-binding domain comprises:
- a heavy chain variable domain of SEQ ID NO:
- 1 and a light chain variable domain of SEQ ID NO:
- 64, SEQ ID NO:
- 70, SEQ ID NO:
- 74, SEQ ID NO:
- 77, SEQ ID NO:
- 78, or SEQ ID NO:
- 79;
- or
- a heavy chain variable domain of SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 20, SEQ ID NO:
- 22, SEQ ID NO:
- 26, SEQ ID NO:
- 40, SEQ ID NO:
- 46, SEQ ID NO:
- 47, SEQ ID NO:
- 48, SEQ ID NO:
- 49, SEQ ID NO:
- 50, SEQ ID NO:
- 51, SEQ ID NO:
- 52, SEQ ID NO:
- 81, SEQ ID NO:
- 82, SEQ ID NO:
- 83, SEQ ID NO:
- 84, SEQ ID NO:
- 85, SEQ ID NO:
- 86, SEQ ID NO:
- 87, SEQ ID NO:
- 88, SEQ ID NO:
- 89, SEQ ID NO:
- 90, SEQ ID NO:
- 91, SEQ ID NO:
- 92, SEQ ID NO:
- 93, SEQ ID NO:
- 94, SEQ ID NO:
- 95, SEQ ID NO:
- 96, SEQ ID NO:
- 97, SEQ ID NO:
- 98, SEQ ID NO:
- 99, or SEQ ID NO:
- 100 and a light chain variable domain of SEQ ID NO:
- 2;
- and wherein:
- (i) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0;
- or
- the dissociation constant (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.0;
- and
- (ii) the composition provides for one or more of:
- an increase in toxin liberation in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC comprising a heavy chain variable domain of SEQ ID NO:
- 1 and a light chain variable domain of SEQ ID NO:
- 2;
- an increase in target mammalian cell killing as compared to a composition comprising the same amount of the control ABPC;
- and
- an increase in endolysosomal delivery in the target mammalian cell as compared to a composition comprising the same amount of the control ABPC.
59 more elements
An antigen-binding protein construct (ABPC) comprising:
- a first antigen-binding domain that is capable of specifically binding CD123 or an epitope of CD123 presented on the surface of a target mammalian cell,
- wherein the first antigen-binding domain comprises:
- a heavy chain variable domain of SEQ ID NO:
- 1 and a light chain variable domain of SEQ ID NO:
- 64, SEQ ID NO:
- 70, SEQ ID NO:
- 74, SEQ ID NO:
- 77, SEQ ID NO:
- 78, or SEQ ID NO:
- 79;
- or
- a heavy chain variable domain of SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 20, SEQ ID NO:
- 22, SEQ ID NO:
- 26, SEQ ID NO:
- 40, SEQ ID NO:
- 46, SEQ ID NO:
- 47, SEQ ID NO:
- 48, SEQ ID NO:
- 49, SEQ ID NO:
- 50, SEQ ID NO:
- 51, SEQ ID NO:
- 52, SEQ ID NO:
- 81, SEQ ID NO:
- 82, SEQ ID NO:
- 83, SEQ ID NO:
- 84, SEQ ID NO:
- 85, SEQ ID NO:
- 86, SEQ ID NO:
- 87, SEQ ID NO:
- 88, SEQ ID NO:
- 89, SEQ ID NO:
- 90, SEQ ID NO:
- 91, SEQ ID NO:
- 92, SEQ ID NO:
- 93, SEQ ID NO:
- 94, SEQ ID NO:
- 95, SEQ ID NO:
- 96, SEQ ID NO:
- 97, SEQ ID NO:
- 98, SEQ ID NO:
- 99, or SEQ ID NO:
- 100 and a light chain variable domain of SEQ ID NO:
- 2;
- and wherein:
- (i) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0;
- or
- (ii) the dissociation constant (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the Kp at a pH of about 7.0 to about 8.0.
49 more elements
An antigen-binding protein construct (ABPC) comprising:
- a first antigen-binding domain that is capable of specifically binding CD123 or an epitope of CD123 presented on the surface of a target mammalian cell;
- and
- a conjugated toxin, radioisotope, drug, or small molecule,
- wherein the first antigen-binding domain comprises:
- a heavy chain variable domain of SEQ ID NO:
- 1 and a light chain variable domain of SEQ ID NO:
- 64, SEQ ID NO:
- 70, SEQ ID NO:
- 74, SEQ ID NO:
- 77, SEQ ID NO:
- 78, or SEQ ID NO:
- 79;
- or
- a heavy chain variable domain of SEQ ID NO:
- 14, SEQ ID NO:
- 15, SEQ ID NO:
- 16, SEQ ID NO:
- 17, SEQ ID NO:
- 20, SEQ ID NO:
- 22, SEQ ID NO:
- 26, SEQ ID NO:
- 40, SEQ ID NO:
- 46, SEQ ID NO:
- 47, SEQ ID NO:
- 48, SEQ ID NO:
- 49, SEQ ID NO:
- 50, SEQ ID NO:
- 51, SEQ ID NO:
- 52, SEQ ID NO:
- 81, SEQ ID NO:
- 82, SEQ ID NO:
- 83, SEQ ID NO:
- 84, SEQ ID NO:
- 85, SEQ ID NO:
- 86, SEQ ID NO:
- 87, SEQ ID NO:
- 88, SEQ ID NO:
- 89, SEQ ID NO:
- 90, SEQ ID NO:
- 91, SEQ ID NO:
- 92, SEQ ID NO:
- 93, SEQ ID NO:
- 94, SEQ ID NO:
- 95, SEQ ID NO:
- 96, SEQ ID NO:
- 97, SEQ ID NO:
- 98, SEQ ID NO:
- 99, or SEQ ID NO:
- 100 and a light chain variable domain of SEQ ID NO:
- 2;
- and wherein:
- (i) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0;
- or
- the dissociation constant (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.0;
- and
- (ii) the composition provides for one or more of:
- an increase in toxin liberation in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC comprising a heavy chain variable domain of SEQ ID NO:
- 1 and a light chain variable domain of SEQ ID NO:
- 2;
- an increase in target mammalian cell killing as compared to a composition comprising the same amount of the control ABPC;
- and
- an increase in endolysosomal delivery in the target mammalian cell as compared to a composition comprising the same amount of the control ABPC.
59 more elements
Dependencies are inferred from the claim text.