	US 12,441,798 B2
	CD123 binding proteins and related compositions and methods
Gabriela Hernandez-Hoyos, Seattle, WA (US); Elaine T. Sewell, Seattle, WA (US); Catherine J. McMahan, Seattle, WA (US); David Bienvenue, Seattle, WA (US); John W. Blankenship, Seattle, WA (US); Danielle Mitchell, Seattle, WA (US); and Peter Pavlik, Seattle, WA (US)
Assigned to Aptevo Research and Development LLC, Seattle, WA (US)
Filed by APTEVO RESEARCH AND DEVELOPMENT LLC, Seattle, WA (US)
Filed on Feb. 15, 2024, as Appl. No. 18/442,779.
Application 18/442,779 is a continuation of application No. 17/557,440, filed on Dec. 21, 2021, granted, now 11,939,392.
Application 17/557,440 is a continuation of application No. 16/335,561, granted, now 11,242,400, issued on Feb. 8, 2022, previously published as PCT/US2017/052808, filed on Sep. 21, 2017.
Claims priority of provisional application 62/466,192, filed on Mar. 2, 2017.
Claims priority of provisional application 62/397,736, filed on Sep. 21, 2016.
Prior Publication US 2024/0343801 A1, Oct. 17, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/28 (2006.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); C07K 16/30 (2006.01); C12N 15/62 (2006.01); A61K 39/00 (2006.01); C07K 16/00 (2006.01)

CPC C07K 16/2809 (2013.01) [A61P 35/00 (2018.01); A61P 35/02 (2018.01); C07K 16/2866 (2013.01); C07K 16/2896 (2013.01); C07K 16/3061 (2013.01); C12N 15/62 (2013.01); A61K 2039/505 (2013.01); A61K 2039/545 (2013.01); C07K 16/005 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/33 (2013.01); C07K 2317/524 (2013.01); C07K 2317/526 (2013.01); C07K 2317/53 (2013.01); C07K 2317/565 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/732 (2013.01); C07K 2317/734 (2013.01); C07K 2317/75 (2013.01); C07K 2317/90 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01)]

15 Claims

1. A method for treating a hematological cancer in a subject, wherein said hematological cancer is characterized by overexpression of CD123, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a recombinant polypeptide comprising a CD123 binding domain and a CD3 binding domain;

wherein the CD123-binding domain comprises (i) an immunoglobulin light chain variable region comprising LCDR1, LCDR2, and LCDR3, and (ii) an immunoglobulin heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein the LCDR1 comprises the amino acid sequence set forth in SEQ ID NO:6; the LCDR2 comprises the amino acid sequence set forth in WAS; the LCDR3 comprises the amino acid sequence set forth in SEQ ID NO:10, the HCDR1 comprises the amino acid sequence set forth in SEQ ID NO:12; the HCDR2 comprises the amino acid sequence set forth in SEQ ID NO:14; and the HCDR3 comprises the amino acid sequence set forth in SEQ ID NO:16; and

wherein the CD3-binding domain comprises: (i) an immunoglobulin light chain variable region comprising LCDR1, LCDR2, and LCDR3, and (ii) an immunoglobulin heavy chain variable region comprising HCDR1, HCDR2, and HCDR3, wherein

(a) the LCDR1, LCDR2 and LCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO:162, SEQ ID NO:163, and SEQ ID NO:164, respectively, and the HCDR1, HCDR2, and HCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO: 165, SEQ ID NO:166, and SEQ ID NO:167, respectively;

(b) the LCDR1, LCDR2 and LCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO:168, DSS, and SEQ ID NO:170, respectively, and the HCDR1, HCDR2, and HCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO: 171, SEQ ID NO:172, and SEQ ID NO:173, respectively;

(c) the LCDR1, LCDR2 and LCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO: 307, SEQ ID NO: 308 and SEQ ID NO:309, respectively, and the HCDR1, HCDR2, and HCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO: 174, SEQ ID NO: 175 and SEQ ID NO:176, respectively;

(d) the LCDR1, LCDR2 and LCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO: 310, GTK and SEQ ID NO: 178, respectively, and the HCDR1, HCDR2, and HCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO: 179, SEQ ID NO: 180 and SEQ ID NO: 181, respectively;

(e) the LCDR1, LCDR2 and LCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO: 182, SEQ ID NO: 183 and SEQ ID NO: 184, respectively, and the HCDR1, HCDR2, and HCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO: 185, SEQ ID NO: 186 and SEQ ID NO: 187, respectively; or

(f) the LCDR1, LCDR2 and LCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO: 188, DTS and SEQ ID NO: 190, respectively, and the HCDR1, HCDR2, and HCDR3 of the CD3-binding domain comprise the amino acid sequences set forth in SEQ ID NO: 191, SEQ ID NO: 192 and SEQ ID NO: 193, respectively.