IP Library › Granted Patent US 12,435,146
Granted Patent B2
US 12,435,146 · App. 18/189,065 · Granted Oct 7, 2025

Anti-Flt-1 antibodies for treating Duchenne muscular dystrophy

Inventors: Dennis Keefe (Lexington, MA); Hans De Haard (Zwijnaarde, BE); Natalie De Jonge (Zwijnaarde, BE); Sofie Gabriels (Zwijnaarde, BE)
Assignee: Shire Human Genetic Therapies, Inc.
C07K16/2863A61K39/39566A61K2039/505C07K2317/22C07K2317/24C07K2317/33C07K2317/34C07K2317/50C07K2317/515C07K2317/55C07K2317/565C07K2317/569C07K2317/70C07K2317/74C07K2317/76C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 12,435,146
App. No.
18/189,065
Granted
Oct 7, 2025
Kind
B2
Abstract

The present invention provides, among other things, anti-Flt-1 antibodies and methods for treating muscular dystrophy, in particular, Duchenne muscular dystrophy (DMD). In some embodiments, a method according to the present invention includes administering to an individual who is suffering from or susceptible to DMD an effective amount of an anti-Flt-1 antibody or antigen-binding protein thereof such that at least one symptom or feature of DMD is reduced in intensity, severity, or frequency, or has delayed onset.

Claims (30)

1. A polynucleotide encoding an anti-Flt-1 antibody or antigen-binding fragment thereof comprising (a) a variable light (VL) chain CDR1 defined by an amino acid sequence having identity to SEQ ID NO: 21, a VL CDR2 defined by an amino acid sequence having identity to SEQ ID NO: 24, a VL CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 26, a variable heavy (VH) chain CDR1 defined by an amino acid sequence having identity to SEQ ID NO: 2, a VH CDR2 defined by an amino acid sequence having identity to SEQ ID NO: 6, and a VH CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 16;

(b) a VL CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 21, a VL CDR2 defined by the amino acid sequence having identity to SEQ ID NO: 24, a VL CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 27, a VH CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 2, a VH CDR2 defined by an amino acid sequence having identity to SEQ ID NO: 7, and a VH CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 17;

(c) a VL CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 21, a VL CDR2 defined by the amino acid sequence having identity to SEQ ID NO: 24, a VL CDR3 defined by the amino acid sequence having identity to SEQ ID NO: 26, a VH CDR1 defined by an amino acid sequence having identity to SEQ ID NO: 3, a VH CDR2 defined by an amino acid sequence having identity to SEQ ID NO: 12, and a VH CDR3 defined by the amino acid sequence having identity to SEQ ID NO: 17;

(d) a VL CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 21, a VL CDR2 defined by the amino acid sequence having identity to SEQ ID NO: 24, a VL CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 28, a VH CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 2, a VH CDR2 defined by an amino acid sequence having identity to SEQ ID NO: 8, and a VH CDR3 defined by the amino acid sequence having identity to SEQ ID NO: 17; or

(e) a VL CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 21, a VL CDR2 defined by the amino acid sequence having identity to SEQ ID NO: 24, a VL CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 32, a VH CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 3, a VH CDR2 defined by the amino acid sequence having identity to SEQ ID NO: 12, and a VH CDR3 defined by the amino acid sequence having identity to SEQ ID NO: 17.

2. An expression vector comprising the polynucleotide of claim 1 .

3. A host cell comprising the polynucleotide of claim 1 or the expression vector of claim 2 .

4. A method of making an antibody or antigen-binding fragment thereof that specifically binds to human Flt-1 comprising culturing the host cell of claim 3 .

5. The polynucleotide encoding an anti-Flt-1 antibody or antigen-binding fragment thereof of claim 1 , comprising

(a) a light chain variable (VL) region comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 60 and a heavy chain variable (VH) region comprising an amino acid sequence having at least 90% identity SEQ ID NO: 45,

(b) a light chain comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 76 and a heavy chain comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 71,

(c) a light chain comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 85 and a heavy chain comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 72,

(d) a light chain comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 84 and a heavy chain comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 71,

(e) a light chain comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 86 and a heavy chain comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 73, or

(f) a light chain comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 83 and a heavy chain comprising an amino acid sequence having at least 90% identity to SEQ ID NO: 70.

6. An expression vector comprising the polynucleotide of claim 5 .

7. A host cell comprising the expression vector of claim 6 .

8. A hybridoma cell producing the anti-Flt-1 antibody or antigen-binding fragment thereof that specifically binds to human Flt-1 comprising one or more complementarity determining regions (CDR) selected from the group consisting of

(a) a variable light (VL) chain CDR1 defined by an amino acid sequence having identity to SEQ ID NO: 21, a VL CDR2 defined by an amino acid sequence having identity to SEQ ID NO: 24, a VL CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 26, a variable heavy (VH) chain CDR1 defined by an amino acid sequence having identity to SEQ ID NO: 2, a VH CDR2 defined by an amino acid sequence having identity to SEQ ID NO: 6, and a VH CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 16;

(b) a VL CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 21, a VL CDR2 defined by the amino acid sequence having identity to SEQ ID NO: 24, a VL CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 27, a VH CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 2, a VH CDR2 defined by an amino acid sequence having identity to SEQ ID NO: 7, and a VH CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 17;

(c) a VL CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 21, a VL CDR2 defined by the amino acid sequence having identity to SEQ ID NO: 24, a VL CDR3 defined by the amino acid sequence having identity to SEQ ID NO: 26, a VH CDR1 defined by an amino acid sequence having identity to SEQ ID NO: 3, a VH CDR2 defined by an amino acid sequence having identity to SEQ ID NO: 12, and a VH CDR3 defined by the amino acid sequence having identity to SEQ ID NO: 17;

(d) a VL CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 21, a VL CDR2 defined by the amino acid sequence having identity to SEQ ID NO: 24, a VL CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 28, a VH CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 2, a VH CDR2 defined by an amino acid sequence having identity to SEQ ID NO: 8, and a VH CDR3 defined by the amino acid sequence having identity to SEQ ID NO: 17; or

(e) a VL CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 21, a VL CDR2 defined by the amino acid sequence having identity to SEQ ID NO: 24, a VL CDR3 defined by an amino acid sequence having identity to SEQ ID NO: 32, a VH CDR1 defined by the amino acid sequence having identity to SEQ ID NO: 3, a VH CDR2 defined by the amino acid sequence having identity to SEQ ID NO: 12, and a VH CDR3 defined by the amino acid sequence having identity to SEQ ID NO: 17.

9. A polynucleotide encoding an anti-Flt-1 antibody or antigen-binding fragment thereof, comprising

(a) a light chain variable (VL) region comprising an amino acid sequence having identity to SEQ ID NO: 60 and a heavy chain variable (VH) region comprising an amino acid sequence having identity SEQ ID NO: 45,

(b) a light chain comprising an amino acid sequence having identity to of SEQ ID NO: 76 and a heavy chain comprising an amino acid sequence having identity to SEQ ID NO: 71,

(c) a light chain comprising an amino acid sequence having identity to SEQ ID NO: 85 and a heavy chain comprising an amino acid sequence having identity to SEQ ID NO: 72,

(d) a light chain comprising an amino acid sequence having identity to SEQ ID NO: 84 and a heavy chain comprising an amino acid sequence having identity to SEQ ID NO: 71,

(e) a light chain comprising an amino acid sequence having identity to SEQ ID NO: 86 and a heavy chain comprising an amino acid sequence having identity to SEQ ID NO: 73, or

(f) a light chain comprising an amino acid sequence having identity to SEQ ID NO: 83 and a heavy chain comprising an amino acid sequence having identity to SEQ ID NO: 70.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 30, 2023
From: KEEFE, DENNIS
To: SHIRE HUMAN GENETIC THERAPIES, INC.
Reel/Frame 063175/0884 →
Continuity (5)
Continuation 16991762 · Aug 12, 2020
Continuation 15564976
Provisional Application 62307645 · Mar 14, 2016
Provisional Application 62144251 · Apr 7, 2015
Related Publication 20240076387A1 · Mar 7, 2024
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