Half-life extending moieties and methods of using the same

Patent metadata

Field	Value
Publication number	US-2024316154-A1
Application number	US-202218259500-A
Country	US
Kind code	A1
Filing date	Feb 1, 2022
Priority date	Feb 2, 2021
Publication date	Sep 26, 2024
Grant date	—

Abstract

The disclosure relates generally to biology and medicine, and more particularly it relates to compounds acting as half-life (t½)-extending moieties for use with therapeutics, especially for improving t½ of biological-based therapeutics (i.e., biotherapeutics or biologics). The disclosure further relates to fusions and conjugates that include one or more of the compounds acting as t½-extending moieties, as well as pharmaceutical compositions including the same and their use in treating various conditions, diseases or disorders.

First claim

The invention claimed is:

1 . A compound comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:1-37 and 124-126, or at least about 90% sequence similarity thereto.

2 - 41 . (canceled)

42 . A compound comprising a structure of:
M-X 1 , X 1 -M, M-L 1 -X 1 , X 1 -L 1 -M, X 1 -M-X 2 , X 2 -M-X 1 , X 1 -L 1 -M-X 2 , X 2 -L 1 -M-X 1 , X 1 -M-L 1 -X 2 , X 2 -M-L 1 -X 1 , X 1 -L 1 -M-L 2 -X 2 , X 2 -L 1 -M-L 2 -X 1 , M-L 1 -X 1 -L 2 -X 2 , M-L 1 -X 2 -L 2 -X 1 , X 1 -L 2 -X 2 -L 1 -M, or X 2 -L 2 -X 1 -L 1 -M, wherein M is an amino acid sequence selected from the group consisting of SEQ ID NOS:1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 124, 125 and 126, or at least about 90% sequence similarity thereto, wherein X 1 is a first biotherapeutic, wherein X 2 (if present) is a second biotherapeutic, wherein L 1 (if present) is a first linker having an amino acid sequence selected from the group consisting of (GGGGQ) n (SEQ ID NO:38), (GGGQ) n (SEQ ID NO:39), (GGGGS) n (SEQ ID NO:40), (PGPQ) n (SEQ ID NO:41), (PGPA) n (SEQ ID NO:42), (GGGG(AP) n GGGG) (SEQ ID NO:43), (GGE) n (SEQ ID NO:44), (GGGGGE) n (SEQ ID NO:45), (GGK) n (SEQ ID NO:46), (GGGGK) n (SEQ ID NO:47), (GGGG(EP) n GGGG) (SEQ ID NO:48), (GGGG(KP) n GGGG) (SEQ ID NO:49), (PGPE) n (SEQ ID NO:50), and (PGPK) n (SEQ ID NO:51), wherein n can be from 1 to 10, and wherein L 2 (if present) is a second linker having an amino acid sequence selected from the group consisting of SEQ ID NOS:64 and 65, or at least about 90% sequence similarity thereto.

43 . The compound of claim 42 , wherein the first biotherapeutic is a peptide, protein or oligomer.

44 . The compound of claim 42 , wherein the second biotherapeutic is a peptide, protein or oligomer.

45 . The compound of claim 42 , wherein the first biotherapeutic and the second biotherapeutic are distinct from one another.

46 . The compound of claim 42 , wherein L 1 has an amino acid sequence selected from the group consisting of SEQ ID NOS:52 to 63, or at least about 90% sequence similarity thereto.

47 . The compound of claim 42 , wherein the first biotherapeutic and/or the second biotherapeutic is a peptide or protein such as an antibody (Ab) or fragment thereof, adrenocorticotropic hormone (ACTH), growth/differentiation factor 15 (GDF15), incretin (INC), insulin (INS), interleukin (IL), ciliary neurotrophic factor (CNTF), neuregulin (NRG) or relaxin (RLN).

48 . The compound of claim 47 , wherein the peptide or protein is an INC.

49 . The compound of claim 48 , wherein the INC is selected from the group consisting of glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1) and GIP/GLP-1.

50 . The compound of claim 47 , wherein the peptide or protein is IL, and wherein the IL is IL-2.

51 . The compound of claim 47 , wherein the peptide or protein is NRG, and wherein the NRG is neuregulin 1 (NRG1) or neuregulin 4 (NRG4).

52 . The compound of claim 47 , wherein the peptide or protein is RLN, and wherein the RLN is relaxin 2 (RLN2).

53 . A pharmaceutical composition comprising a compound of claim 42 and a pharmaceutically acceptable buffer.

54 . The pharmaceutical composition of claim 53 further comprising an additional therapeutic agent.

55 . A method of treating an individual, the method comprising the step of:
administering to the individual an effective amount of a compound of claim 42 .

56 . A compound of claim 1 for use in extending the t½ of a biotherapeutic.

57 - 59 . (canceled)

60 . A compound comprising any one of SEQ ID NOS: 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117 or 118, or at least about 90% sequence similarity thereto.

61 . A pharmaceutical composition comprising a compound of claim 60 and a pharmaceutically acceptable buffer.

62 . The pharmaceutical composition of claim 61 further comprising an additional therapeutic agent.

63 . A method of treating an individual, the method comprising the step of:
administering to the individual an effective amount of a compound of claim 60 .

64 - 66 . (canceled)

Assignees

• Lilly Co Eli

Inventors

• Ferrante Andrea
• Heuer Josef George
• Lee Stacey Lynn
• Verdino Petra

Classifications

• C07K14/00

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K38/2221

  Relaxins · CPC title

• A61K38/2013

  IL-2 · CPC title

• A61K38/1883

  Neuregulins, e.g.. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor · CPC title