IP Library Granted Patent US 12,227,777
Granted Patent B2
US 12,227,777 · App. 16/961,525 · Granted Feb 18, 2025

Soluble alpha-Klotho proteins, protein fragments, and uses thereof

Inventor: Moosa Mohammadi (Scarsdale, NY)
Assignee: NEW YORK UNIVERSITY
C12N9/2402A61K38/00C12Y302/01031
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,227,777
App. No.
16/961,525
Granted
Feb 18, 2025
Kind
B2
Abstract

Disclosed herein are modified soluble α-Klotho proteins and isolated fragments of wildtype soluble α-Klotho protein. Also disclosed are pharmaceutical compositions including the modified soluble α-Klotho proteins and/or isolated fragments of soluble α-Klotho protein and methods of their use in treating a subject.

Claims (8)

1. A modified soluble α-Klotho protein, wherein the modified soluble α-Klotho protein comprises a KL2 extracellular domain comprising a modification to eliminate binding affinity of the modified soluble α-Klotho protein for fibroblast growth factor receptor (FGFR) 1c, FGFR3c, and/or FGFR4, as compared to a wildtype soluble α-Klotho protein, wherein the wildtype soluble α-Klotho protein comprises the amino acid sequence of E34 to S981 of SEQ ID NO: 1, and wherein the modified soluble α-Klotho protein comprises the amino acid sequence of E34 to S932 of SEQ ID NO:2 or E34 to S959 of SEQ ID NO: 7.

2. The modified soluble α-Klotho protein according to claim 1 , wherein the modified soluble α-Klotho protein binds fibroblast growth factor (FGF) 23.

3. A pharmaceutical composition comprising the modified soluble α-Klotho protein according to claim 1 and a pharmaceutically acceptable carrier.

4. The modified soluble α-Klotho protein according to claim 1 , wherein the modified soluble α-Klotho protein comprises the amino acid sequence of E34 to S932 of SEQ ID NO:2.

5. The modified soluble α-Klotho protein according to claim 1 , wherein the modified soluble α-Klotho protein comprises the amino acid sequence of E34 to S959 of SEQ ID NO:7.

6. A modified soluble α-Klotho protein possessing a modification as compared to a wildtype soluble α-Klotho protein, wherein the modified soluble α-Klotho protein comprises the amino acid sequence of E34 to S932 of SEQ ID NO:2 or E34 to S959 of SEQ ID NO:7.

7. The modified soluble α-Klotho protein according to claim 6 , wherein the modified soluble α-Klotho protein comprises the amino acid sequence of E34 to S932 of SEQ ID NO:2.

8. The modified soluble α-Klotho protein according to claim 6 , wherein the modified soluble α-Klotho protein comprises the amino acid sequence of E34 to S959 of SEQ ID NO:7.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 31, 2020
From: MOHAMMADI, MOOSA
To: NEW YORK UNIVERSITY
Reel/Frame 053645/0529 →
Continuity (2)
Provisional Application 62616945 · Jan 12, 2018
Related Publication 20210054355A1 · Feb 25, 2021
References Cited (23)
US 8889426B2 · Mohammadi et al. · 2014 [cited by applicant]
US 8889621B2 · Mohammadi et al. · 2014 [cited by applicant]
US 8999929B2 · Mohammadi et al. · 2015 [cited by applicant]
US 9272017B2 · Mohammadi et al. · 2016 [cited by applicant]
US 9464126B2 · Mohammadi et al. · 2016 [cited by applicant]
US 9474785B2 · Mohammadi et al. · 2016 [cited by applicant]
US 9475856B2 · Mohammadi et al. · 2016 [cited by applicant]
US 9550820B2 · Mohammadi et al. · 2017 [cited by applicant]
US 9657075B2 · Mohammadi et al. · 2017 [cited by applicant]
US 9907830B2 · Mohammadi et al. · 2018 [cited by applicant]
US 9926355B2 · Mohammadi et al. · 2018 [cited by applicant]
US 9926356B2 · Mohammadi et al. · 2018 [cited by applicant]
US 10174090B2 · Mohammadi et al. · 2019 [cited by applicant]
US 10364278B2 · Mohammadi et al. · 2019 [cited by applicant]
US 10464979B2 · Mohammadi et al. · 2019 [cited by applicant]
US 10632180B2 · Dubal · 2020 [cited by examiner]
US 10633424B2 · Mohammadi et al. · 2020 [cited by applicant]
US 10654909B2 · Guo · 2020 [cited by examiner]
US 10703788B2 · Mohammadi et al. · 2020 [cited by applicant]
US 20150079065A1 · Wolf et al. · 2015 [cited by applicant]
International Search Report and Written Opinion for corresponding PCT International Application No. PCT/US19/13282 (mailed Jun. 17, 2019). [cited by applicant]
Goetz & Mohammadi, “Exploring Mechanisms of FGF Signaling Through the Lens of Structural Biology,” Nat. Rev. Mol. Cell Biol. 14(3):166-180 (2013). [cited by applicant]
Chen et al., “α-Klotho is a Non-Enzymatic Molecular Scaffold for FGF23 Hormone Signaling,” Nature 553(7689): 461-466 (2018). [cited by applicant]