	US 12,116,411 B2
	Antibodies binding to human CD3 at acidic pH
Hiep Tran, West Chester, PA (US); Carla Campbell, Royersford, PA (US); Byung Lee, Watertown, MA (US); Fouad Moussa, Allentown, PA (US); Andrew Phillips, Pottstown, PA (US); Rajesh Singh, Malvern, PA (US); and Laura DeCristofano, Phoenixville, PA (US)
Assigned to Abzyme Therapeutics LLC, Pottstown, PA (US)
Filed by Abzyme Therapeutics LLC, Pottstown, PA (US)
Filed on Nov. 2, 2021, as Appl. No. 17/517,258.
Claims priority of provisional application 63/109,005, filed on Nov. 3, 2020.
Prior Publication US 2022/0135680 A1, May 5, 2022
Int. Cl. C07K 16/28 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01)

CPC C07K 16/2809 (2013.01) [A61K 39/3955 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07K 2317/24 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/92 (2013.01)]

15 Claims

1. An isolated antibody or antigen-binding fragment comprising light and heavy chain variable regions of an anti-CD3-epsilon antibody, or a variant thereof with binding activity to human CD3, comprising:

CDR-H1 that comprises SEQ ID NO: 1;

CDR-H3 that comprises SEQ ID NO: 4;

CDR-L2 that comprises SEQ ID NO: 8; and

CDR-L3 that comprises SEQ ID NO: 9 or SEQ ID NO: 10;

wherein one or both of the following (1) or (2) applies:

(1) CDR-H2 that comprises SEQ ID NO: 3; or

(2) CDR-L1 that comprises SEQ ID NO: 7;

wherein if (1) does not apply CDR-H2 comprises SEQ ID NO:2; and

wherein if (2) does not apply CDR-L1 comprises SEQ ID NO: 5 or SEQ ID NO: 6;

and

wherein the antibody or antigen-binding fragment activates T cells at pH 6.2 comparable to non-mutated OKT3 in the presence of a CD28 agonist while having 2-fold or more reduced activity compared to non-mutated OKT3 at pH 7.4 as measured in a T-cell activation assay.