US5846528A
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Treating anemia using recombinant adeno-associated virus virions comprising an EPO DNA sequence
Assignee: Genzyme Corp
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Filing: 1997-01-16
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Granted: 1998-12-08
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Expires: 2017-01-16
Abstract
Abstract The use of recombinant adeno-associated virus (AAV) virions for delivery of DNA molecules to muscle cells and tissue in the treatment of anemia is disclosed. The invention allows for the direct, in vivo injection of recombinant AAV virions into muscle tissue, e.g., by intramuscular injection, as well as for the in vitro transduction of muscle cells which can subsequently be introduced into a subject for treatment. The invention provides for sustained, high-level expression of a delivered nucleotide sequence encoding erythropoietin, and for in vivo secretion thereof from transduced muscle cells such that systemic delivery is achieved.
Inventors
- 👤 Gregory M. Podsakoff
- 👤 Gary J. Kurtzman
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 22:51
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/63; C12N15/79; C12N15/85; C12N15/86; A; A61; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/18; A61K38/1816; A61K38/43; A61K38/46; A61K38/47; A61K48/00; A61K48/005; A61K48/0058; A61K48/0075; A61P; A61P7/00; A61P7/06; C07; C07K; C07K14/00; C07K14/435; C07K14/475; C07K14/505; C12N9/00; C12N9/14; C12N9/24; C12N9/2402; C12Y; C12Y302/00; C12Y302/01; C12Y302/0102; C12Y302/01023; A01; A01K; A01K2217/00; A01K2217/05; C12N2750/00; C12N2750/00011; C12N2750/14011; C12N2750/14111; C12N2750/14141; C12N2750/14143; C12N2830/00; C12N2830/42; C12N2840/00; C12N2840/44
Claims Analysis
Total Claims: 37
Claim 1
Independent Claim
37 words
A composition, comprising: (a) recombinant AAV virions which comprise an AAV vector containing a nucleic acid molecule encoding erythropoietin operably linked to control elements that direct the transcription and translation thereof; and (b) a pharmaceutically acceptable excipient.
Claim 2
Dependent Claim
37 words
A composition, comprising: (a) recombinant AAV virions which comprise an AAV vector containing a nucleic acid molecule encoding erythropoietin operably linked to control elements that direct the transcription and translation thereof; and (b) a pharmaceutically acceptable excipient.
Claim 3
Dependent Claim
63 words
A method of treating anemia in a mammalian subject, said method comprising administering to muscle of said subject a therapeutically effective amount of the pharmaceutical composition of claim 1 such that said recombinant AAV virions transduce muscle cells in said subject, and said nucleic acid molecule is expressed by said transduced cells at a level sufficient to increase a hematocrit of said subject.
Claim 4
Dependent Claim
30 words
The method of claim 2, wherein the anemia is an anemic disorder selected from the group consisting of anemia associated with chronic renal failure, cancer, cancer chemotherapy and antiviral therapy.
Claim 5
Dependent Claim
64 words
A method of treating a hemoglobinopathy in a mammalian subject, said method comprising administering to muscle of said subject a therapeutically effective amount of the pharmaceutical composition of claim 1 such that said recombinant AAV virions transduce muscle cells in said subject, and said nucleic acid molecule is expressed by said transduced cells at a level sufficient to increase a hematocrit of said subject.
Claim 6
Dependent Claim
20 words
The method of claim 4, wherein the hemoglobinopathy is selected from the group consisting of sickle cell disease and thalassemia.
Claim 7
Dependent Claim
14 words
The method of claim 2, wherein the muscle cells are derived from skeletal muscle.
Claim 8
Dependent Claim
12 words
The method of claim 6, wherein the muscle cells are skeletal myoblasts.
Claim 9
Dependent Claim
12 words
The method of claim 6, wherein the muscle cells are skeletal myocytes.
Claim 10
Dependent Claim
14 words
The method of claim 2, wherein the pharmaceutical composition is administered by intramuscular injection.
Claim 11
Dependent Claim
15 words
The method of claim 9, wherein the pharmaceutical composition is administered in a single dose.
Claim 12
Dependent Claim
14 words
The method of claim 9, wherein the pharmaceutical composition is administered in multiple doses.
Claim 13
Dependent Claim
14 words
The method of claim 2, wherein the nucleic acid molecule encodes native human erythropoietin.
Claim 14
Dependent Claim
14 words
The method of claim 2, wherein the nucleic acid molecule encodes native feline erythropoietin.
Claim 15
Dependent Claim
14 words
The method of claim 2, wherein the control elements comprise a muscle-specific promoter sequence.
Claim 16
Dependent Claim
14 words
The method of claim 2, wherein the control elements comprise an inducible promoter sequence.
Claim 17
Dependent Claim
21 words
The method of claim 2, wherein the pharmaceutical composition is administered to the subject in combination with an adjunctive pharmacological therapy.
Claim 18
Dependent Claim
31 words
The method of claim 16, wherein the adjunctive pharmacological therapy comprises administering a therapeutically effective amount of an agent selected from the group consisting of hydroxyurea, butyrate, clotrimazole, and combinations thereof.
Claim 19
Independent Claim
118 words
A method of treating anemia in a mammalian subject, said method comprising: (a) introducing recombinant AAV virions into muscle cells in vitro to produce transduced muscle cells, wherein said recombinant AAV virions comprise an AAV vector having a nucleic acid molecule encoding erythropoietin operably linked to control elements that direct the transcription and translation thereof when present in muscle of said subject; and (b) administering directly into muscle of said subject a therapeutically effective amount of a composition comprising the transduced muscle cells from step (a) to deliver said transduced cells to muscle of said subject, whereafter said nucleic acid molecule is expressed by said transduced cells at a level sufficient to increase a hematocrit of said subject.
Claim 20
Independent Claim
118 words
A method of treating anemia in a mammalian subject, said method comprising: (a) introducing recombinant AAV virions into muscle cells in vitro to produce transduced muscle cells, wherein said recombinant AAV virions comprise an AAV vector having a nucleic acid molecule encoding erythropoietin operably linked to control elements that direct the transcription and translation thereof when present in muscle of said subject; and (b) administering directly into muscle of said subject a therapeutically effective amount of a composition comprising the transduced muscle cells from step (a) to deliver said transduced cells to muscle of said subject, whereafter said nucleic acid molecule is expressed by said transduced cells at a level sufficient to increase a hematocrit of said subject.
Claim 21
Dependent Claim
30 words
The method of claim 18, wherein the anemia is an anemic disorder selected from the group consisting of anemia associated with chronic renal failure, cancer, cancer chemotherapy and antiviral therapy.
Claim 22
Dependent Claim
11 words
The method of claim 18, wherein the anemia is a hemoglobinopathy.
Claim 23
Dependent Claim
20 words
The method of claim 20, wherein the hemoglobinopathy is selected from the group consisting of sickle cell disease and thalassemia.
Claim 24
Dependent Claim
14 words
The method of claim 18, wherein the muscle cells are derived from skeletal muscle.
Claim 25
Dependent Claim
12 words
The method of claim 22, wherein the muscle cells are skeletal myoblasts.
Claim 26
Dependent Claim
12 words
The method of claim 22, wherein the muscle cells are skeletal myocytes.
Claim 27
Dependent Claim
14 words
The method of claim 18, wherein the nucleic acid molecule encodes native human erythropoietin.
Claim 28
Dependent Claim
14 words
The method of claim 18, wherein the nucleic acid molecule encodes native feline erythropoietin.
Claim 29
Dependent Claim
14 words
The method of claim 18, wherein the control elements comprise a muscle-specific promoter sequence.
Claim 30
Dependent Claim
14 words
The method of claim 18, wherein the control elements comprise an inducible promoter sequence.
Claim 31
Dependent Claim
65 words
A method for delivering erythropoietin systemically to a mammalian subject, said method comprising administering directly into muscle of said subject the pharmaceutical composition of claim 1 such that said recombinant AAV virions transduce muscle cells in said subject and said nucleic acid molecule is expressed by said transduced cells to produce a systemic level of erythropoietin, thereby providing for an increased hematocrit of said subject.
Claim 32
Dependent Claim
14 words
The method of claim 29, wherein the nucleic acid molecule encodes native human erythropoietin.
Claim 33
Dependent Claim
14 words
The method of claim 29, wherein the nucleic acid molecule encodes native feline erythropoietin.
Claim 34
Independent Claim
124 words
A method for delivering erythropoietin systemically to a mammalian subject, said method comprising: (a) introducing recombinant AAV virions into muscle cells in vitro to produce transduced muscle cells, wherein said recombinant AAV virions comprise an AAV vector having a nucleic acid molecule encoding erythropoietin operably linked to control elements that direct the transcription and translation thereof when present in muscle of said subject; and (b) administering directly into muscle of said subject a therapeutically effective amount of a composition comprising the transduced muscle cells from step (a) to deliver said transduced cells to muscle of said subject, whereafter said nucleic acid molecule is expressed by said transduced cells to produce a systemic level of erythropoietin, thereby providing for an increased hematocrit of said subject.
Claim 35
Independent Claim
124 words
A method for delivering erythropoietin systemically to a mammalian subject, said method comprising: (a) introducing recombinant AAV virions into muscle cells in vitro to produce transduced muscle cells, wherein said recombinant AAV virions comprise an AAV vector having a nucleic acid molecule encoding erythropoietin operably linked to control elements that direct the transcription and translation thereof when present in muscle of said subject; and (b) administering directly into muscle of said subject a therapeutically effective amount of a composition comprising the transduced muscle cells from step (a) to deliver said transduced cells to muscle of said subject, whereafter said nucleic acid molecule is expressed by said transduced cells to produce a systemic level of erythropoietin, thereby providing for an increased hematocrit of said subject.
Claim 36
Dependent Claim
14 words
The method of claim 32, wherein the nucleic acid molecule encodes native human erythropoietin.
Claim 37
Dependent Claim
14 words
The method of claim 32, wherein the nucleic acid molecule encodes native feline erythropoietin.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2001-12-07 | 2002-06-08 | 2002-12-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-12-07 | 2006-06-08 | 2006-12-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-12-07 | 2010-06-08 | 2010-12-08 | $7700.00 | Window Closed / Lapsed |