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US 2026/0209386 A1Published application
Ptk7-binding proteins with ph-dependent binding and uses thereof
AssigneeMythic Therapeutics, Inc.
InventorsNimish Gera, Brian P. Fiske, Alexander J. Nichols, Lihui Xu
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Abstract
Provided herein are antigen-binding protein constructs (ABPCs) that bind PTK7 and uses of the same.
Claims72
A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising:
- a first antigen-binding domain (ABD) that is capable of specifically binding PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein:
- the dissociation rate of the first ABD at a pH of ~4.0-6.5 is faster than the dissociation rate at a pH of ~7.0-8.0;
- and/or the KD of the first ABD at a pH of ~4.0-6.5 is greater than the KD at a pH of ~7.0-8.0;
- and optionally wherein the ABPC exhibits increased target-specific uptake by cancer cells expressing PTK7 relative to the uptake by the same cells of a suitable control ABPC.
1 more element
A composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising:
- a first ABD that is capable of specifically binding PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell;
- and a conjugated toxin, radioisotope, drug, or small molecule,
- wherein:
- (a) the dissociation rate of the first ABD at a pH of ~4.0-6.5 is faster than the dissociation rate at a pH of ~7.0-8.0;
- or the dissociation constant (KD) of the first ABD at a pH of ~4.0-6.5 is greater than the KD at a pH of ~7.0-8.0;
- and
- (b) the composition provides for one or more of:
- (i) an increase in toxin liberation in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC;
- (ii) an increase in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC;
- or (iii) an increase in endolysosomal delivery in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC.
7 more elements
An antigen-binding protein construct (ABPC) comprising:
- a first antigen-binding domain (ABD) that is capable of specifically binding PTK7 or an epitope of PTK7 presented on the surface of a target mammalian cell, wherein:
- the dissociation rate of the first ABD at a pH of ~4.0-6.5 is faster than the dissociation rate at a pH of ~7.0-8.0;
- or the KD of the first ABD at a pH of ~4.0-6.5 is greater than the KD at a pH of ~7.0-8.0.
The ABPC of 57 or 58, wherein the HCVD and/or LCVD optionally includes a histidine at two or more positions in its defining SEQ ID NO.
Dependencies are inferred from the claim text.