US 12,721,900 B2Granted

Non-viral immuno-targeting

AssigneeUniversity of Washington

InventorsNicholas P. Whitehead, Stanley C. Froehner

Life of this patent

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Abstract

The disclosure provides compositions and methods for delivering a payload to cells or tissues that express GLUT4. In some embodiments, the compositions comprise an antibody, or fragment or derivative thereof, that specifically binds to glucose transporter 4 (“GLUT4”) protein, and a therapeutic payload conjugated thereto. In some exemplary embodiments, the compositions are useful for methods of treating a disease or condition in a subject with a genetic mutation in a gene encoding dystrophin protein, wherein the payload comprises a nucleic acid encoding a functional dystrophin protein or functional fragment thereof to ameliorate aspects of the disease.

Claims17

Dependent claims

A method of treating a disease or condition in a subject with a genetic mutation in a gene encoding dystrophin protein, comprising administering to a subject a therapeutically effective amount of a composition comprising:

(a) an antibody, or fragment or derivative thereof, that specifically binds glucose transporter 4 (“GLUT4”) protein;
and
(b) a therapeutic payload conjugated to the antibody, or fragment or derivative thereof, wherein the therapeutic payload comprises a nucleic acid with a promoter sequence operatively linked to a sequence encoding a dystrophin protein, or a functional fragment thereof;
wherein the antibody, or fragment or derivative thereof, that specifically binds GLUT4 protein comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:
i) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
10, a VH-CDR2 having a sequence set forth in SEQ ID NO:18, and a VH-CDR3 having a sequence LDF;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:34, a VL-CDR2 having a sequence set forth in SEQ ID NO:42, and a VL-CDR3 having a sequence set forth in SEQ ID NO:50;
ii) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
11, a VH-CDR2 having a sequence set forth in SEQ ID NO:19, and a VH-CDR3 having a sequence set forth in SEQ ID NO:27;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:35, a VL-CDR2 having a sequence set forth in SEQ ID NO:43, and a VL-CDR3 having a sequence set forth in SEQ ID NO:51;
iii) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
12, a VH-CDR2 having a sequence set forth in SEQ ID NO:20, and a VH-CDR3 having a sequence set forth in SEQ ID NO:28;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:36, a VL-CDR2 having a sequence set forth in SEQ ID NO:44, and a VL-CDR3 having a sequence set forth in SEQ ID NO:52;
iv) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
13, a VH-CDR2 having a sequence set forth in SEQ ID NO:21, and a VH-CDR3 having a sequence set forth in SEQ ID NO:29;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:37, a VL-CDR2 having a sequence set forth in SEQ ID NO:45, and a VL-CDR3 having a sequence set forth in SEQ ID NO:53;
v) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
14, a VH-CDR2 having a sequence set forth in SEQ ID NO:22, and a VH-CDR3 having a sequence set forth in SEQ ID NO:30;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:38, a VL-CDR2 having a sequence set forth in SEQ ID NO:46, and a VL-CDR3 having a sequence set forth in SEQ ID NO:54;
vi) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
15, a VH-CDR2 having a sequence set forth in SEQ ID NO:23, and a VH-CDR3 having a sequence set forth in SEQ ID NO:31;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:39, a VL-CDR2 having a sequence set forth in SEQ ID NO:47, and a VL-CDR3 having a sequence set forth in SEQ ID NO:55;
vii) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
16, a VH-CDR2 having a sequence set forth in SEQ ID NO:24, and a VH-CDR3 having a sequence set forth in SEQ ID NO:32;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:40, a VL-CDR2 having a sequence set forth in SEQ ID NO:48, and a VL-CDR3 having a sequence set forth in SEQ ID NO:56;
or
viii) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
17, a VH-CDR2 having a sequence set forth in SEQ ID NO:25, and a VH-CDR3 having a sequence set forth in SEQ ID NO:33;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:41, a VL-CDR2 having a sequence set forth in SEQ ID NO:49, and a VL-CDR3 having a sequence set forth in SEQ ID NO:57.

26 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/625,722Filed 9 Jul 2020 · us provisional application
Priority: 10 Jul 2019
Published: US 2022/0280652 A18 Sep 2022
Granted: 1 Sep 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification16 codes

A61K 47/6849
The modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site: the antibody targeting a receptor, a cell…
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61K 9/127
Dispersions; Emulsions: synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 38/1719
From mammals: muscle proteins, e.g. myosin or actin

Family

Application62/872,425Us provisional application · filed 10 Jul 2019
US 2022/0280652 A1Pre-grant publication · published 8 Sep 2022
US 12,721,900 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

(a) an antibody, or fragment or derivative thereof, that specifically binds glucose transporter 4 (“GLUT4”) protein;
and
(b) a therapeutic payload conjugated to the antibody, or fragment or derivative thereof, wherein the therapeutic payload comprises a nucleic acid with a promoter sequence operatively linked to a sequence encoding a dystrophin protein, or a functional fragment thereof;
wherein the antibody, or fragment or derivative thereof, that specifically binds GLUT4 protein comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein:
i) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
10, a VH-CDR2 having a sequence set forth in SEQ ID NO:18, and a VH-CDR3 having a sequence LDF;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:34, a VL-CDR2 having a sequence set forth in SEQ ID NO:42, and a VL-CDR3 having a sequence set forth in SEQ ID NO:50;
ii) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
11, a VH-CDR2 having a sequence set forth in SEQ ID NO:19, and a VH-CDR3 having a sequence set forth in SEQ ID NO:27;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:35, a VL-CDR2 having a sequence set forth in SEQ ID NO:43, and a VL-CDR3 having a sequence set forth in SEQ ID NO:51;
iii) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
12, a VH-CDR2 having a sequence set forth in SEQ ID NO:20, and a VH-CDR3 having a sequence set forth in SEQ ID NO:28;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:36, a VL-CDR2 having a sequence set forth in SEQ ID NO:44, and a VL-CDR3 having a sequence set forth in SEQ ID NO:52;
iv) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
13, a VH-CDR2 having a sequence set forth in SEQ ID NO:21, and a VH-CDR3 having a sequence set forth in SEQ ID NO:29;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:37, a VL-CDR2 having a sequence set forth in SEQ ID NO:45, and a VL-CDR3 having a sequence set forth in SEQ ID NO:53;
v) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
14, a VH-CDR2 having a sequence set forth in SEQ ID NO:22, and a VH-CDR3 having a sequence set forth in SEQ ID NO:30;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:38, a VL-CDR2 having a sequence set forth in SEQ ID NO:46, and a VL-CDR3 having a sequence set forth in SEQ ID NO:54;
vi) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
15, a VH-CDR2 having a sequence set forth in SEQ ID NO:23, and a VH-CDR3 having a sequence set forth in SEQ ID NO:31;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:39, a VL-CDR2 having a sequence set forth in SEQ ID NO:47, and a VL-CDR3 having a sequence set forth in SEQ ID NO:55;
vii) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
16, a VH-CDR2 having a sequence set forth in SEQ ID NO:24, and a VH-CDR3 having a sequence set forth in SEQ ID NO:32;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:40, a VL-CDR2 having a sequence set forth in SEQ ID NO:48, and a VL-CDR3 having a sequence set forth in SEQ ID NO:56;
or
viii) the VH comprises a VH-CDR1 having a sequence set forth in SEQ ID NO:
17, a VH-CDR2 having a sequence set forth in SEQ ID NO:25, and a VH-CDR3 having a sequence set forth in SEQ ID NO:33;
and the VL comprises a VL-CDR1 having a sequence set forth in SEQ ID NO:41, a VL-CDR2 having a sequence set forth in SEQ ID NO:49, and a VL-CDR3 having a sequence set forth in SEQ ID NO:57.

26 more elements

Facts

Application

17/625,722Filed 9 Jul 2020 · us provisional application

Priority

10 Jul 2019

Published

US 2022/0280652 A18 Sep 2022

Granted

1 Sep 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification16 codes

A61K 47/6849
The modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site: the antibody targeting a receptor, a cell…
A61K 9/0019
Galenical forms characterised by the site of application: injectable compositions; Intramuscular, intravenous, arterial, subcutaneous…
A61K 9/127
Dispersions; Emulsions: synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 38/1719
From mammals: muscle proteins, e.g. myosin or actin