Granted Patent
B2
US 12,600,756 · App. 17/939,238 · Granted Apr 14, 2026
Recombinant modified fibroblast growth factors and therapeutic uses thereof
Inventors:
David Eveleth (San Diego, CA); Jennifer Jenkins-Eveleth (San Diego, CA); Amuthakannan Subramaniam (San Diego, CA); Ralph Bradshaw (Encinitas, CA)
Assignee:
TREFOIL THERAPEUTICS, INC.
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Abstract
Described herein are modified fibroblast growth factor (FGF) polypeptides, pharmaceutical compositions and medicaments that include such modified FGF polypeptides, and methods of using such modified FGF polypeptides to treat or prevent conditions that benefit from administration of FGFs.
Claims (19)
1 . A method of treating a corneal injury in a patient, the method comprising administering to the patient a recombinant modified FGF-1 polypeptide comprising an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 206 while retaining Ser at amino acid position 16, Cys at amino acid position 66, and Val at amino acid position 117, and having an N-terminal methionine residue positioned upstream to the first residue of SEQ ID NO: 206, wherein the corneal injury is induced by exposure to a vesicant as a gas or vapor, and the first dose is administered within 48 hours of exposure to the vesicant, thereby reducing corneal epithelial cell and/or corneal endothelial cell injury.
2 . The method of claim 1 , wherein the corneal injury comprises a corneal endothelial injury.
3 . The method of claim 2 , wherein long term degeneration of the cornea is reduced.
4 . The method of claim 2 , wherein loss of corneal endothelial cells is reduced.
5 . The method of claim 1 , wherein the corneal injury comprises a stromal injury.
6 . The method of claim 5 , wherein stromal scarring and corneal opacity are reduced.
7 . The method of claim 1 , wherein the corneal injury comprises mustard gas keratopathy (MGK).
8 . The method of claim 7 , wherein administration of the recombinant modified FGF-1 polypeptide results in amelioration of histopathological conditions associated with MGK.
9 . The method of claim 8 , wherein the histopathological conditions include hyperplasia of corneal epithelial layer and epithelial-stromal cell separation.
10 . The method of claim 1 , wherein corneal edema and corneal erosion are reduced.
11 . The method of claim 10 , wherein the corneal erosion is characterized by de-epithelialization of the cornea.
12 . The method of claim 11 , wherein administration of the recombinant modified FGF-1 polypeptide results in reduction of the severity of corneal de-epithelialization.
13 . The method of claim 11 , wherein administration of the recombinant modified FGF-1 polypeptide results in faster re-epithelialization of the cornea.
14 . The method of claim 1 , wherein the vesicant is selected from the group consisting of: sulfur mustard (SM), nitrogen mustard (NM), lewisite, and half mustard (2-chloroethyl ethyl sulfide (CEES)).
15 . The method of claim 1 , wherein the vesicant is nitrogen mustard (NM) and administration of the recombinant modified FGF-1 polypeptide results in suppression of NM-induced up-regulation of a disintegrin and metalloprotease 17 (ADAM17).
16 . The method of claim 1 , wherein the recombinant FGF-1 polypeptide comprises an amino acid sequence that has at least 95% sequence identity to the recombinant modified FGF-1 polypeptide of SEQ ID NO: 2.
17 . The method of claim 1 , wherein the recombinant FGF-1 polypeptide comprises an amino acid sequence according to SEQ ID NO: 2.
18 . The method of claim 1 , wherein administration of the recombinant modified FGF-1 polypeptide results in reduction in corneal edema.
19 . The method of claim 1 , wherein the recombinant modified FGF-1 polypeptide is administered over a period of up to two weeks or until complete regeneration of the corneal epithelium.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Sep 7, 2022
From: EVELETH, DAVID; JENKINS-EVELETH, JENNIFER; SUBRAMANIAM, AMUTHAKANNAN; BRADSHAW, RALPH
To: TREFOIL THERAPEUTICS, INC.
Reel/Frame 061013/0208 →
Continuity (5)
Division
16611182
Provisional Application
62584624
· Nov 10, 2017
Provisional Application
62502540
· May 5, 2017
Provisional Application
62502529
· May 5, 2017
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