Il12 receptor agonists and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2025066441-A1
Application number	US-202218580810-A
Country	US
Kind code	A1
Filing date	Jul 18, 2022
Priority date	Jul 19, 2021
Publication date	Feb 27, 2025
Grant date	—

Abstract

The present disclosure relates to IL 12 receptor agonists with improved therapeutic profiles.

First claim

1 .- 53 . (canceled)

54 . An IL12 receptor agonist comprising a first polypeptide chain comprising a first Fc domain, an IL 12 p35 moiety, and an IL12 p40 moiety, wherein the IL12 p40 moiety comprises a p40 D2 domain and a p40 D3 domain and does not comprise a p40 D1 domain.

55 . The IL12 receptor agonist of claim 54 , further comprising a second polypeptide chain comprising a second Fc domain associated with the first Fc domain to form an Fc dimer.

56 . The IL12 receptor agonist of claim 55 , wherein the first polypeptide chain comprises, in an N- to C-terminal orientation, the IL12 p35 moiety, the IL12 p40 moiety, and the first Fc domain.

57 . The IL12 receptor agonist of claim 55 , wherein the first polypeptide chain comprises, in an N- to C-terminal orientation, the IL12 p40 moiety, the IL12 p35 moiety, and the first Fc domain.

58 . The IL12 receptor agonist of claim 57 , wherein the second polypeptide chain further comprises a second targeting moiety or targeting moiety component N-terminal to the second Fc domain.

59 . The IL12 receptor agonist of claim 58 , wherein the IL12 p40 moiety comprises a sequence having at least 90% sequence identity to amino acids 129 to 328 of SEQ ID NO: 5.

60 . The IL12 receptor agonist of claim 58 , wherein the IL12 p40 moiety comprises amino acids 129 to 328 of SEQ ID NO: 5.

61 . The IL12 receptor agonist of claim 59 , wherein the IL12 p35 moiety comprises a sequence having at least 90% sequence identity to amino acids 23 to 219 of SEQ ID NO: 6.

62 . The IL12 receptor agonist of claim 60 , wherein the IL12 p35 moiety comprises amino acids 23 to 219 of SEQ ID NO: 6.

63 . The IL12 receptor agonist of claim 55 , wherein the first polypeptide chain further comprises a first targeting moiety or targeting moiety component.

64 . The IL12 receptor agonist of claim 63 , wherein the first polypeptide chain comprises, in an N- to C-terminal orientation, the first targeting moiety or targeting moiety component, the first Fc domain, the IL12 p35 moiety, and the IL12 p40 moiety.

65 . The IL12 receptor agonist of claim 63 , wherein the first polypeptide chain comprises, in an N- to C-terminal orientation, the first targeting moiety or targeting moiety component, the first Fc domain, the IL12 p40 moiety, and the IL12 p35 moiety.

66 . The IL12 receptor agonist of claim 65 , wherein the second polypeptide chain further comprises a second targeting moiety or targeting moiety component N-terminal to the second Fc domain.

67 . The IL12 receptor agonist of claim 65 , wherein the IL12 p40 moiety comprises a sequence having at least 90% sequence identity to amino acids 129 to 328 of SEQ ID NO: 5.

68 . The IL12 receptor agonist of claim 67 , wherein the IL12 p40 moiety comprises amino acids 129 to 328 of SEQ ID NO: 5.

69 . The IL12 receptor agonist of claim 67 , wherein the IL12 p35 moiety comprises a sequence having at least 90% sequence identity to amino acids 23 to 219 of SEQ ID NO: 6.

70 . The IL12 receptor agonist of claim 68 , wherein the IL12 p35 moiety comprises amino acids 23 to 219 of SEQ ID NO: 6.

71 . A pharmaceutical composition comprising the IL12 receptor agonist of claim 54 and an excipient.

72 . A method of locally inducing an immune response in a target tissue, the method comprising administering to a subject in need thereof the IL12 receptor agonist of claim 54 .

73 . A method of locally inducing an immune response in a target tissue, the method comprising administering to a subject in need thereof an IL12 receptor agonist, wherein the IL12 receptor agonist comprises:
(a) a first polypeptide chain comprising a first Fc domain, an IL12 p35 moiety, and an IL12 p40 moiety, wherein the IL12 p40 moiety comprises a p40 D2 domain and a p40 D3 domain and does not comprise a p40 D1 domain; and (b) a second polypeptide chain comprising a targeting moiety or targeting moiety component and a second Fc domain associated with the first Fc domain to form an Fc dimer.

Assignees

• Regeneron Pharma

Inventors

• Chang Aaron
• Wu Jiaxi
• Zhang Tong
• Bloch Nicolin
• Ullman Erica
• Smith Eric
• Lin Chia-Yang
• Davis Samuel

Classifications

• C07K2317/30

  characterized by aspects of specificity or valency · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title

• C07K2317/75

  Agonist effect on antigen · CPC title