Claims for Patent: 10,357,571

Summary for Patent: 10,357,571

Title:	Development of masked therapeutic antibodies to limit off-target effects
Abstract:	In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a masked monoclonal antibody (mAb) is provided, which includes a therapeutic mAb and a mask, the mask comprising protein A and protein L attached by a protease cleavable linker.
Inventor(s):	Williams; John C. (Monrovia, CA), Zer; Cindy (Duarte, CA), Avery; Kendra N. (Pasadena, CA), Rodeck; Ulrich (Philadelphia, PA), Donaldson; Joshua M. (Lumberton, NJ), Kari; Csaba (Rosemont, CA)
Assignee:	Thomas Jefferson University (Philadelphia, PA) City of Hope (Duarte, CA)
Application Number:	14/949,648
Patent Claims:	1. A cross-masked monoclonal antibody (mAb) complex comprising: (1) a first masked mAb comprising: (a) a first masking epitope comprising amino acid residues 23-198 of SEQ ID NO:5 as shown in FIG. 14; (b) a first linker that is cleavable by a protease specific to a target tissue, wherein the protease is matrix metalloproteinase-9 (MMP-9); and (c) a first antibody or a first antigen-binding fragment thereof that binds EGFR, wherein the antibody is cetuximab, and (2) a second masked mAb comprising: (a) a second masking epitope comprising amino acid residues 23-198 of SEQ ID NO:6 as shown in FIG. 15; (b) a second linker that is cleavable by the protease specific to the target tissue, wherein the protease is MMP-9; and (c) a second antibody or a second antigen-binding fragment thereof that binds EGFR, wherein the antibody is matuzumab. 2. The cross-masked mAb complex of claim 1, wherein the first masked mAb and the second masked mAb form a dimer by occlusion of the first and second antigen recognition sites by the second and first masking epitopes, respectively. 3. The cross-masked mAb complex of claim 1, wherein the first linker and the second linker comprise the amino acid sequence VPLSLYS (SEQ ID NO:3). 4. The cross-masked mAb complex of claim 3, wherein the first linker and the second linker comprise the amino acid sequence SEQ ID NO: 4 or SEQ ID NO: 7. 5. The cross-masked mAb complex of claim 1, wherein the first masked mAb comprises a first signal sequence and the second masked mAb comprises a second signal sequence. 6. The cross-masked mAb complex of claim 5, wherein the first masked mAb comprises the amino acid sequence of SEQ ID NO:5. 7. The cross-masked mAb complex of claim 5, wherein the first masked mAb is encoded by the nucleic acid sequence of SEQ ID NO:1. 8. The cross-masked mAb complex of claim 5, wherein the second masked mAb comprises the amino acid sequence of SEQ ID NO:6, wherein the amino acid sequence of SEQ ID NO: 6 comprises amino acid P at position 175 and N at position 176.

Details for Patent 10,357,571

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2030-08-03
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2030-08-03