US 12,234,271 B2
Il-2 conjugates and methods of use to treat autoimmune diseases
Jerod Ptacin, La Jolla, CA (US); Carolina E. Caffaro, La Jolla, CA (US); and Marcos Milla, La Jolla, CA (US)
Assigned to Synthorx, Inc., La Jolla, CA (US)
Filed by Synthorx, Inc., La Jolla, CA (US)
Filed on Sep. 9, 2020, as Appl. No. 17/016,003.
Claims priority of provisional application 63/042,393, filed on Jun. 22, 2020.
Claims priority of provisional application 62/953,075, filed on Dec. 23, 2019.
Claims priority of provisional application 62/930,987, filed on Nov. 5, 2019.
Claims priority of provisional application 62/900,488, filed on Sep. 14, 2019.
Claims priority of provisional application 62/898,478, filed on Sep. 10, 2019.
Prior Publication US 2021/0070827 A1, Mar. 11, 2021
Int. Cl. C07K 14/55 (2006.01); A61P 37/06 (2006.01); C07D 487/04 (2006.01)
CPC C07K 14/55 (2013.01) [A61P 37/06 (2018.01); C07D 487/04 (2013.01)] 57 Claims
 
1. An IL-2 conjugate comprising an IL-2 polypeptide having the amino acid sequence of SEQ ID NO: 3 or 4 in which at least one amino acid residue in the IL-2 polypeptide is replaced by the structure of Formula (I):

OG Complex Work Unit Chemistry
wherein:
Z is CH2 and Y is

OG Complex Work Unit Chemistry
Y is CH2 and Z is

OG Complex Work Unit Chemistry
Z is CH2 and Y is

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or
Y is CH2 and Z is

OG Complex Work Unit Chemistry
W is a PEG group having a molecular weight selected from about 5 kDa, 10 kDa, 15 kDa, 20 kDa, 25 kDa, 30 kDa, 35 kDa, 40 kDa, 45 kDa, 50 kDa, 55 kDa, and 60 kDa;
X has the structure:

OG Complex Work Unit Chemistry
X−1 indicates the point of attachment to the preceding amino acid residue; and
X+1 indicates the point of attachment to the following amino acid residue;
wherein when the IL-2 conjugate comprises the amino acid sequence of SEQ ID NO: 3, the at least one amino acid residue replaced by the structure of Formula (I) is located in the IL-2 polypeptide at a position selected from P1, T2, S3, S4, S5, T6, K7, K8, Q10, L11, E14, H15, L17, L18, D19, Q21, M22, N25, G26, N28, N29, Y30, K31, M45, P46, K47, A49, T50, E51, L52, K53, H54, Q56, E66, Q73, S74, K75, N76, F77, H78, R80, P81, R82, D83, S86, N87, 188, V90, 191, L93, E94, K96, G97, S98, E99, T100, T101, F102, E105, A107, D108, E109, T110, A111, T112, E115, N118, R119, T122, F123, S124, Q125, S126, S129, T130, L131, and T132; or
wherein when the IL-2 conjugate comprises the amino acid sequence of SEQ ID NO: 4, the at least one amino acid replaced by the structure of Formula (I) is located in the IL-2 polypeptide at a position selected from A1, P2, T3, S4, S5, S6, T7, K8, K9, Q11, L12, E15, H16, L18, L19, D20, Q22, M23, N26, G27, N29, N30, Y31, K32, M46, P47, K48, A50, T51, E52, L53, H55, Q57, [E60,] E67, Q74, S75, K76, N77, F78, H79, R81, P82, R83, D84, S87, N88, 189, V91, 192, L94, E95, K97, G98, S99, E100, T101, T102, F103, E106, A108, D109, E110, T111, A112, T113, E116, N119, R120, T123, S125, Q126, S127, S130, T131, L132, and T133.