IP Library Granted Patent US 12,497,632
Granted Patent B2
US 12,497,632 · App. 17/265,750 · Granted Dec 16, 2025

Clinical parameters by expression of factor VIII

Inventors: Edward R. Conner (Brisbane, CA); Brigit E. Riley (Brisbane, CA); Didier Rouy (Brisbane, CA)
Assignee: Sangamo Therapeutics, Inc.
C12N15/86A61K38/37A61P7/04C12N7/00A61K48/00C12N2750/14043C12N2750/14071
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Quick Facts
Patent No.
US 12,497,632
App. No.
17/265,750
Granted
Dec 16, 2025
Kind
B2
Abstract

Described herein are constructs used for liver-specific expression of a transgene.

Claims (29)

1 . A method of increasing Factor VIII (FVIII) protein in a human subject, comprising intravenously administering to the human subject a dose of 1×10 13 to 5×10 13 vg/kg of an Adenovirus-Associated Virus serotype 6 (AAV6) vector that encodes a FVIII protein, wherein administration of the AAV6 vector results in a clinically relevant 20% to 172% increase in the level of circulating FVIII activity, and wherein the AAV6 vector comprises an expression cassette that comprises

a first insulator sequence comprising nucleotides 14-32 of SEQ ID NO:5,

an enhancer sequence of SEQ ID NO:2,

a promoter sequence of SEQ ID NO:3,

a coding sequence that encodes an FVIII protein of SEQ ID NO:1, and

a second insulator sequence comprising nucleotides 4869-4885 of SEQ ID NO:5.

2 . The method of claim 1 , wherein administration of the AAV6 vector results in one or zero occurrences of spontaneous bleeding episodes in the human subject between 3-12 months after administration.

3 . The method of claim 1 , comprising administering a dose of 1×10 13 vg/kg to 3×10 13 vg/kg of the AAV6 vector.

4 . The method of claim 1 , comprising administering a dose of 2×10 13 vg/kg to 4×10 13 vg/kg of the AAV6 vector.

5 . The method of claim 1 , comprising administering a dose of 3×10 13 vg/kg of the AAV6 vector.

6 . The method of claim 1 , wherein the clinically relevant increase is a 20% to 150% increase.

7 . The method of claim 1 , wherein the AAV6 vector comprises an AAV2 5′ inverted terminal repeat (ITR) sequence and an AAV2 3′ ITR sequence that flank the expression cassette.

8 . The method of claim 7 , wherein the AAV2 5′ ITR comprises the nucleotide sequence of SEQ ID NO:12 and/or the AAV2 3′ ITR comprises the nucleotide sequence of SEQ ID NO:13.

9 . The method of claim 1 , wherein the expression cassette comprises the nucleotide sequence of SEQ ID NO:5.

10 . The method of claim 1 , wherein the human subject has hemophilia.

11 . A method of decreasing spontaneous bleeding episodes in a human subject receiving FVIII therapy, comprising intravenously administering to the human subject a dose of 1×10 13 to 5×10 13 vg/kg of an Adenovirus-Associated Virus serotype 6 (AAV6) vector that encodes a FVIII protein, wherein no more than one spontaneous bleeding episode occurs from 3 to 12 months after the intravenous administration, and wherein the AAV6 vector comprises an expression cassette that comprises

a first insulator sequence comprising nucleotides 14-32 of SEQ ID NO:5,

an enhancer sequence of SEQ ID NO:2,

a promoter sequence of SEQ ID NO:3,

a coding sequence that encodes an FVIII protein of SEQ ID NO:1, and

a second insulator sequence comprising nucleotides 4869-4885 of SEQ ID NO:5.

12 . The method of claim 11 , wherein the human subject does not receive any FVIII treatments 3-12 months after administration.

13 . The method of claim 11 , comprising administering a dose of 1×10 13 vg/kg to 3×10 13 vg/kg of the AAV6 vector.

14 . The method of claim 11 , comprising administering a dose of 2×10 13 vg/kg to 4×10 13 vg/kg of the AAV6 vector.

15 . The method of claim 11 , comprising administering a dose of 3×10 13 vg/kg of the AAV6 vector.

16 . The method of claim 11 , wherein the human subject does not receive any FVIII treatments 2, 5, or 10 years after administration.

17 . The method of claim 11 , wherein the AAV6 vector comprises an AAV2 5′ ITR sequence and an AAV2 3′ ITR sequence that flank the expression cassette.

18 . The method of claim 17 , wherein the AAV2 5′ ITR comprises the nucleotide sequence of SEQ ID NO:12 and/or the AAV2 3′ ITR comprises the nucleotide sequence of SEQ ID NO:13.

19 . The method of claim 12 , wherein the human subject has hemophilia and wherein the expression cassette comprises the nucleotide sequence of SEQ ID NO:5.

Assignments (6)
CHANGE OF ADDRESS Recorded Sep 25, 2025
From: SANGAMO THERAPEUTICS, INC.
To: SANGAMO THERAPEUTICS, INC.
Reel/Frame 072935/0212 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 22, 2021
From: CONNER, EDWARD R.; RILEY, BRIGIT E.; ROUY, DIDIER
To: SANGAMO THERAPEUTICS, INC.
Reel/Frame 056948/0726 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 22, 2021
From: RILEY, BRIGIT E.; ROUY, DIDIER
To: SANGAMO THERAPEUTICS, INC.
Reel/Frame 056948/0777 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 22, 2021
From: RILEY, BRIGIT E.; ROUY, DIDIER
To: SANGAMO THERAPEUTICS, INC.
Reel/Frame 056948/0847 →
EMPLOYMENT AGREEMENT Recorded Jul 22, 2021
From: CONNER, EDWARD R.
To: SANGAMO BIOSCIENCES, INC.
Reel/Frame 056963/0202 →
CHANGE OF NAME Recorded Jul 22, 2021
From: SANGAMO BIOSCIENCES, INC.
To: SANGAMO THERAPEUTICS, INC.
Reel/Frame 056963/0300 →
Continuity (4)
Provisional Application 62869445 · Jul 1, 2019
Provisional Application 62826887 · Mar 29, 2019
Provisional Application 62714553 · Aug 3, 2018
Related Publication 20210171982A1 · Jun 10, 2021
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