Methods for treating rheumatoid arthritis and multiple sclerosis using MCP1 fusions
View Patent ↗The present invention provides polypeptides including MCP1 fused, optionally, by a linker, to an immunoglobulin. Methods for using the polypeptides to treat medical disorders are also covered.
1. A method for treating rheumatoid arthritis, in a subject, comprising administering, to the subject, a therapeutically effective amount of an isolated polypeptide comprising a human MCP1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2 fused to a human immunoglobulin gamma-1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 7.
2. The method of claim 1 wherein the polypeptide comprising the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide comprises one human MCP1polypeptide fused to one human immunoglobulin gamma-1 polypeptide.
3. The method of claim 2 wherein the polypeptides are fused by a peptide linker.
4. The method of claim 1 wherein the polypeptide comprising the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide is in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
5. The method of claim 1 wherein the polypeptide comprising the human MCP1 polypeptide and the immunoglobulin gamma-1 polypeptide is administered to the subject in association with one or more further therapeutic agents.
6. The method of claim 5 wherein the further therapeutic agent is a member selected from the group consisting of valdecoxib; triamcinolone acetonide; tolmetin; tiaprofenic acid; tenoxicam; tazarotene; sulindac; sulfasalazine; salicylic acid; rofecoxib; prednicarbate; piroxicam, salsalate; phenylbutazone; petroleum jelly; penicillamine; oxaprozin; oilated oatmeal; naproxen; nabumetone; mycophenolate mofetil; mometasone furoate; metronidazole; methotrexate; mesalamine; meloxicam; mefenamic acid; meclofenamate; lumiracoxib; ketorolac; ketoprofen; isotretinoin; injectable gold; infliximab; indomethacin; ibuprofen; hydroxyurea; hydroxychloroquine; hydrocortisone; halobetasol propionate; halcinonide; gold sodium thiomalate; fluticasone propionate; flurbiprofen; flurandrenolide; fluocinonide; fluocinolone acetonide; floctafenine; fenoprofen; etoricoxib; etodolac; etanercept; epsom salts; efalizumab; diflunisal; diflorasone diacetate; diclofenac; desoximetasone; desonide; Dead Sea salts; cyclosporine; coal tar; clobetasol propionate; ciprofloxacin; chloroquine; celecoxib; calcipotriene; budesonide; betamethasone valerate; betamethasone dipropionate; betamethasone benzoate; azathioprine; aurothioglucose; auranofin; aspirin; anthralin; anakinra; amcinonide; aloe vera; alefacept; alclometasone dipropionate; adalimumab; acitretin; ABX-IL8; a mixture of hydrocortisone, dexamethasone, methylprednisolone and prednisolone; a dietary vitamin B12 supplement; a dietary folate supplement; a dietary calcium supplement; 6-Thioguanine; and 6-mercaptopurine.
7. The method of claim 1 wherein the polypeptide comprising the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide is administered in association with one or more further therapeutic procedures.
8. The method of claim 1 wherein the polypeptide comprising the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide is administered in association with a non-steroidal anti-inflammatory drug or a COX-2 inhibitor.
9. The method of claim 1 for treating rheumatoid arthritis in a human subject comprising administering, to the subject, a therapeutically effective amount of an isolated polypeptide comprising one human MCP1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2 fused to one human immunoglobulin gamma-1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 7; wherein the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide are fused by a peptide linker; wherein the polypeptide comprising the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide are in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
10. The method of claim 9 wherein the subject is administered the polypeptide comprising the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide in association with a non-steroidal anti-inflammatory drug or a COX-2 inhibitor.
11. The method of claim 9 wherein the polypeptide comprising the MCP1 polypeptide and the immunoglobulin polypeptide is administered in association with one or more further chemotherapeutic agents selected from the group consisting of methotrexate; aspirin; diclofenac; diflunisal; etodolac; fenoprofen; floctafenine; flurbiprofen; ibuprofen; indomethacin; ketoprofen; ketorolac; meclofenamate; mefenamic acid; meloxicam; nabumetone; naproxen; oxaprozin; phenylbutazone; piroxicam; salsalate; sulindac; tenoxicam; tiaprofenic acid; tolmetin; celecoxib; rofecoxib; valdecoxib; lumiracoxib; etoricoxib; efalizumab; adalimumab; infliximab; and ABX-IL8.
12. The method of claim 11 wherein the further chemotherapeutic agent is infliximab.
13. The method of claim 11 wherein the further chemotherapeutic agent is methotrexate.
14. The method of claim 9 wherein one or more procedures selected from the group consisting of :
a joint X-ray;
a rheumatoid factor blood test;
a test to detect elevated erythrocyte sedimentation rate (ESR);
a blood test to detect low hematocrit;
a blood test to detect abnormal platelet counts;
a blood test to check for C-reactive protein; and
synovial fluid analysis;
are performed on the subject.
15. A method for delaying onset of multiple sclerosis, in a subject, comprising administering, to the subject, a therapeutically effective amount of an isolated polypeptide comprising a human MCP1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2 fused to a human immunoglobulin gamma-1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 7.
16. The method of claim 15 wherein the polypeptide comprising the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide comprises one human MCP1 polypeptide fused to one human immunoglobulin gamma-1 polypeptide.
17. The method of claim 16 wherein the polypeptides are fused by a peptide linker.
18. The method of claim 15 wherein the polypeptide comprising the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide is in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
19. The method of claim 15 wherein the polypeptide comprising the human MCP1 polypeptide and the immunoglobulin gamma-1 polypeptide is administered to the subject in association with one or more further therapeutic agents.
20. The method of claim 19 wherein the further therapeutic agent is a member selected from the group consisting of valdecoxib; triamcinolone acetonide; tolmetin; tiaprofenic acid; tenoxicam; tazarotene; sulindac; sulfasalazine; salicylic acid; rofecoxib; prednicarbate; piroxicam, salsalate; phenylbutazone; petroleum jelly; penicillamine; oxaprozin; oilated oatmeal; naproxen; nabumetone; mycophenolate mofetil; mometasone furoate; metronidazole; methotrexate; mesalamine; meloxicam; mefenamic acid; meclofenamate; lumiracoxib; ketorolac; ketoprofen; isotretinoin; injectable gold; infliximab; indomethacin; ibuprofen; hydroxyurea; hydroxychloroquine; hydrocortisone; halobetasol propionate; halcinonide; gold sodium thiomalate; fluticasone propionate; flurbiprofen; flurandrenolide; fluocinonide; fluocinolone acetonide; floctafenine; fenoprofen; etoricoxib; etodolac; etanercept; epsom salts; efalizumab; diflunisal; diflorasone diacetate; diclofenac; desoximetasone; desonide; Dead Sea salts; cyclosporine; coal tar; clobetasol propionate; ciprofloxacin; chloroquine; celecoxib; calcipotriene; budesonide; betamethasone valerate; betamethasone dipropionate; betamethasone benzoate; azathioprine; aurothioglucose; auranofin; aspirin; anthralin; anakinra; amcinonide; aloe vera; alefacept; alclometasone dipropionate; adalimumab; acitretin; ABX-IL8; a mixture of hydrocortisone, dexamethasone, methylprednisolone and prednisolone; a dietary vitamin B12 supplement; a dietary folate supplement; a dietary calcium supplement; 6-Thioguanine; and 6-mercaptopurine.
21. The method of claim 15 wherein the polypeptide comprising the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide is administered in association with one or more further therapeutic procedures.
22. The method of claim 15 for delaying onset of multiple sclerosis in a human subject comprising administering, to the subject, a therapeutically effective amount of an isolated polypeptide comprising one human MCP1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2 fused to one human immunoglobulin gamma-1 polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 7; wherein the human MCP1 polypeptide and the human immunoglobulin gamma-1 peptide are fused by a peptide linker; and wherein the polypeptide comprising the human MCP1 polypeptide and the human immunoglobulin gamma-1 polypeptide are in a pharmaceutical composition comprising a pharmaceutically acceptable carrier.