Compositions comprising variants and fusions of FGF19 polypeptides

Patent metadata

Field	Value
Publication number	US-11066454-B2
Application number	US-201816216402-A
Country	US
Kind code	B2
Filing date	Dec 11, 2018
Priority date	Nov 28, 2012
Publication date	Jul 20, 2021
Grant date	Jul 20, 2021

Abstract

The invention relates to variants and fusions of fibroblast growth factor 19 (FGF19), variants and fusions of fibroblast growth factor 21 (FGF21), fusions of fibroblast growth factor 19 (FGF19) and/or fibroblast growth factor 21 (FGF21), and variants or fusions of fibroblast growth factor 19 (FGF19) and/or fibroblast growth factor 21 (FGF21) proteins and peptide sequences (and peptidomimetics), having one or more activities, such as glucose lowering activity, and methods for and uses in treatment of hyperglycemia and other disorders.

First claim

What is claimed is:

1. A peptide having an amino acid sequence comprising or consisting of:

(SEQ ID NO: 141)

DSSPLVHYGWGDPIRLRHLYTSGPHGLSSCFLRIRADGVVDCARGQSAHS

LLEIKAVALRTVAIKGVHSVRYLCMGADGKMQGLLQYSEEDCAFEEEIRP

DGYNVYRSEKHRLPVSLSSAKQRQLYKNRGFLPLSHFLPMLPMVPEEPED

LRGHLESDMFSSPLETDSMDPFGLVTGLEAVRSPSFEK,

wherein the peptide has at least one amino acid substitution to the RP sequence of the EIRPD sequence (amino acids 97-101 of SEQ ID NO:141),
wherein the at least one amino acid substitution is (i) a substitution of the R residue to L residue, (ii) a substitution of the P residue to E residue, or (iii) a substitution of the R residue to L residue and a substitution of the P residue to E residue.

2. The peptide of claim 1 , wherein the substitution of the R residue is a R to L substitution.

3. The peptide of claim 1 , wherein the substitution of the P residue is a P to E substitution.

4. The peptide of claim 1 , wherein the substitution of the R residue is a R to L substitution and the substitution of the P residue is a P to E substitution.

5. A pharmaceutical composition, comprising the peptide of claim 1 , and a pharmaceutically acceptable carrier.

6. A nucleic acid molecule encoding a peptide having an amino acid sequence comprising:

(SEQ ID NO: 141)

DSSPLVHYGWGDPIRLRHLYTSGPHGLSSCFLRIRADGVVDCARGQSAHS

LLEIKAVALRTVAIKGVHSVRYLCMGADGKMQGLLQYSEEDCAFEEEIRP

DGYNVYRSEKHRLPVSLSSAKQRQLYKNRGFLPLSHFLPMLPMVPEEPED

LRGHLESDMFSSPLETDSMDPFGLVTGLEAVRSPSFEK,

wherein the peptide has at least one amino acid substitution to the RP sequence of the EIRPD sequence (amino acids 97-101 of SEQ ID NO:141),
wherein the at least one amino acid substitution is (i) a substitution of the R residue to L residue, (ii) a substitution of the P residue to E residue, or (iii) a substitution of the R residue to L residue and a substitution of the P residue to E residue.

7. The nucleic acid molecule of claim 6 , further comprising an expression control element in operable linkage that confers expression of the nucleic acid molecule encoding the peptide in vitro, in a cell or in vivo.

8. A vector comprising the nucleic acid molecule of claim 7 .

9. The vector of claim 8 , wherein the vector comprises a viral vector.

10. A transformed or host cell comprising the vector of claim 8 .

Assignees

• Ngm Biopharmaceuticals Inc

Inventors

• Ling Lei
• Lindhout Darrin Anthony

Classifications

• C07K14/50 Primary

  Fibroblast growth factor [FGF] · CPC title

• A61K38/1825

  Fibroblast growth factor [FGF] · CPC title

• C07K2319/00

  Fusion polypeptide · 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

• A61K45/06

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