Method and apparatus for treatment of cardiac disorders

• US 20060251641A1
• Filed: 05/09/2005
• Published: 11/09/2006
• Est. Priority Date: 05/09/2005
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Keimel, John G.
• Granted Patent: US 8,500,720 B2
• Time in Patent Office: Days
• US Class Current: 424/94.610
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61M 2210/125 Heart
• CPC Class Codes: A61M 39/0208 Subcutaneous access sites for injecting or removing fluids transcutaneous access sites A61M39/0247; implantable infusion devices A61M5/14276
• CPC Class Codes: A61M 39/04 having pierceable self-sealing members
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/172 electrical or electronic A61M5/16804, A61M5/16831 take precedence

Abstract

The present invention is directed to systems and methods for delivering therapy for a cardiac disorder, wherein the system comprises a source for supplying a protein formulation containing a protein that is otherwise deficient in cardiac cells in a patient with a cardiac disorder, and a catheter having a proximal end and a distal end for delivering the protein formulation to the pericardial sac region of a human heart.

Claims

1. An implantable system for delivering therapy for a cardiac disorder;

the system comprising;

a source for supplying a protein formulation containing a protein in a form that is deficient in cardiac cells in a patient with the cardiac disorder; and

a catheter having a proximal end connected to the source and a distal end inserted into a pericardial sac for delivering the protein formulation from the source directly to the pericardial sac.

2. The system of claim 1, wherein the cardiac disorder treated is selected from a group consisting of protein deficiency diseases, enzyme deficiency diseases, inborn errors of metabolism, cardiodegenerative diseases, pericardial diseases, hereditary cardiomyopathy diseases, hereditary channelopathy diseases, protein deficiencies caused by RNA interference therapy, protein deficiencies caused by environmental factors, and combinations thereof.

3. The system of claim 1, wherein the protein formulation is selected from a group consisting of alpha-L-iduronidase, sulfoiduranate sulfate, beta-galactosidase, aryl sulfatase B, N-acetylglucosamine-1-phosphotransferase, glucocerebrosidase, alpha-galactosidase, lysosomal acid alpha-glucosidase, amylo-1,6-glucosidase, long-chain acyl-CoA dehydrogenase, glyoxylate amino transferase, D-glyceric acid dehydrogenase, hepatic mitochondrial 26-hydroxylase, WD gene, copper transporting ATPase enzyme, cystathionine beta-synthase, triose-phosphate isomerase, antithrombin, uridine-5-mono-phosphate synthase, prealbumin, phytanic acid alpha-hydroxylase, myosin heavy chain, myosin binding protein C, cardiac troponin T, KVLQT1, MinK, HERG, MiRP1, nav1.5, Kir2.1, dystrophin, tafazzin, actin, desmin, δ

-sarcoglycan, β

-myosin heavy chain, metavinculin, α

-tropomyosin, titin, β

-sarcoglyan, mitochondrial respiratory chain protein, ryanodine receptor, desmoplakin, plakoglobin, desmoplakin, and combinations thereof.

4. The system of claim 1, wherein the protein formulation comprises proteins that are found in cardiac cells.

5. The system of claim 1, wherein at least some of the proteins within the protein formulation have been modified to include a transport aid and a linker species that provide for enhanced cellular uptake of the protein formulation.

6. The system of claim 1, wherein the source further includes an inlet for the introduction of the protein formulation into the source.

7. The system of claim 1, wherein the source includes an access port.

8. The system of claim 1, wherein the source includes a pump.

9. The system of claim 8, wherein the pump further comprises a refillable reservoir to store the protein formulation prior to delivery to the pericardial sac.

10. The system of claim 8, wherein the pump provides for a programmable delivery rate of the protein formulation, wherein the delivery rate is selected based on factors selected from a group consisting of a specific cardiac disorder, genetic sequence of a patient'"'"'s gene encoding for a protein to be delivered, body weight, and combinations thereof.

15. The apparatus of claim 11, wherein the source further includes an inlet for the introduction of the protein formulation into the source.

16. The apparatus of claim 15, wherein the pump delivers a dosage of the protein formulation via the implantable catheter to the pericardial sac region of the heart at a precise level for a period of time greater than about 24 hours.

17. The apparatus of claim 15, wherein the pump further includes a refillable reservoir to store the protein formulation prior to delivery to the pericardial sac.

11. An apparatus comprising:

an implantable source; and

an implantable catheter for delivering a therapeutic protein formulation from the source to a pericardial sac region of a heart in a patient with a cardiac disorder.

12. The apparatus of claim 11, wherein the therapeutic protein formulation is selected from a group consisting of alpha-L-iduronidase, sulfoiduranate sulfate, beta-galactosidase, aryl sulfatase B, N-acetylglucosamine-1-phosphotransferase, glucocerebrosidase, alpha-galactosidase, lysosomal acid alpha-glucosidase, amylo-1,6-glucosidase, long-chain acyl-CoA dehydrogenase, glyoxylate amino transferase, D-glyceric acid dehydrogenase, hepatic mitochondrial 26-hydroxylase, WD gene, copper transporting ATPase enzyme, cystathionine beta-synthase, triose-phosphate isomerase, antithrombin, uridine-5-mono-phosphate synthase, prealbumin, phytanic acid alpha-hydroxylase, myosin heavy chain, myosin binding protein C, cardiac troponin T, KVLQT1, MinK, HERG, MiRP1, nav1.5, Kir2.1, dystrophin, tafazzin, actin, desmin, δ

-sarcoglycan, β

-myosin heavy chain, metavinculin, α

-tropomyosin, titin, β

-sarcoglyan, mitochondrial respiratory chain protein, ryanodine receptor, desmoplakin, plakoglobin, desmoplakin, and combinations thereof.

13. The apparatus of claim 11, wherein the protein formulation comprises proteins that are found in cardiac cells.

14. The apparatus of claim 11, wherein at least some proteins within the protein formulation have been modified to comprise a transport aid and a linker species that provides for enhanced cellular uptake of the protein formulation.

18. A method for treating cardiac disorders comprising:

injecting a therapeutic protein formulation into an implantable source; and

delivering the therapeutic protein formulation from the source through an implantable catheter directly to a pericardial sac region of a heart.

19. The method of claim 18, wherein the cardiac disorders treated are selected from a group consisting of protein deficiency diseases, enzyme deficiency diseases, inborn errors of metabolism, cardiodegenerative diseases, pericardial diseases, hereditary cardiomyopathy diseases, hereditary channelopathy diseases, protein deficiencies caused by RNA interference therapy, protein deficiencies caused by environmental factors, and combinations thereof.

20. The method of claim 18, wherein the therapeutic protein formulation is selected from the group consisting of alpha-L-iduronidase, sulfoiduranate sulfate, beta-galactosidase, aryl sulfatase B, N-acetylglucosamine-1-phosphotransferase, glucocerebrosidase, alpha-galactosidase, lysosomal acid alpha-glucosidase, amylo-1,6-glucosidase, long-chain acyl-CoA dehydrogenase, glyoxylate amino transferase, D-glyceric acid dehydrogenase, hepatic mitochondrial 26-hydroxylase, WD gene, copper transporting ATPase enzyme, cystathionine beta-synthase, triose-phosphate isomerase, antithrombin, uridine-5-mono-phosphate synthase, prealbumin, phytanic acid alpha-hydroxylase, myosin heavy chain, myosin binding protein C, cardiac troponin T, KVLQT1, MinK, HERG, MiRP1, nav1.5, Kir2.1, dystrophin, tafazzin, actin, desmin, δ

-sarcoglycan, β

-myosin heavy chain, metavinculin, α

-tropomyosin, titin, β

-sarcoglyan, mitochondrial respiratory chain protein, ryanodine receptor, desmoplakin, plakoglobin, desmoplakin, and combinations thereof.

21. The method of claim 18, wherein the protein formulation comprise proteins that are found in cardiac cells.

22. The method of claim 18, wherein at least some of the therapeutic protein formulation has been modified to comprise a transport aid and a linker species that provide for enhanced cellular uptake of the protein formulation.

23. The method of claim 18, wherein integrity and activity of the protein formulation is maintained by adding to the protein formulation, at least one species operable for maintaining a desired pH.

24. The method of claim 18, wherein the source is a pump.

25. The method of claim 24, wherein the pump includes a refillable reservoir to store the protein formulation prior to delivery to the pericardial sac.

26. The method of claim 24, wherein the implantable pump provides for a programmable delivery rate of the protein formulation, wherein the delivery rate is selected based on factors selected from a group consisting of a specific cardiac disorder, genetic sequence of a patient'"'"'s gene encoding for a protein to be delivered, body weight, and combinations thereof.