B7-H4 fusion proteins and methods of use thereof
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07K-014/705
A61K-038/17
C07K-016/28
G01N-033/68
A61K-009/00
A61K-039/44
A61K-038/00
출원번호
US-0679497
(2015-04-06)
등록번호
US-9957312
(2018-05-01)
발명자
/ 주소
Langermann, Solomon
Liu, Linda
Podojil, Joseph R.
Miller, Stephen D.
Marshall, Shannon
출원인 / 주소
MedImmune, LLC
대리인 / 주소
Hunter-Ensor, Melissa
인용정보
피인용 횟수 :
0인용 특허 :
101
초록▼
Fusion proteins containing B7-H4 polypeptides are disclosed. The B7-H4 fusion proteins can include full-length B7-H4 polypeptides, or can contain a fragment of a full-length B7-H4 polypeptide, including some or all of the extracellular domain of the B7-H4 polypeptide. Methods for using the fusion pr
Fusion proteins containing B7-H4 polypeptides are disclosed. The B7-H4 fusion proteins can include full-length B7-H4 polypeptides, or can contain a fragment of a full-length B7-H4 polypeptide, including some or all of the extracellular domain of the B7-H4 polypeptide. Methods for using the fusion proteins to downregulate T cell activation and for the treatment of inflammatory and autoimmune diseases and disorders are also disclosed. The B7-H4 fusion proteins are useful for treating inflammation by inhibiting or reducing differentiation, proliferation, activity, and/or cytokine production and/or secretion by ThI, ThI 7, Th22, and/or other cells that secrete, or cause other cells to secrete, inflammatory molecules, including, but not limited to, IL-1β, TNF-α, TGF-beta, IFN-γ, IL-17, IL-6, IL-23, IL-22, IL-21, and MMPs; or enhancing IL-IO secretion by Tregs, increasing the differentiation of Tregs, increasing the number of Tregs, or combinations thereof.
대표청구항▼
1. A method for reducing inflammation in a human subject, the method comprising treating the subject according to a dosage regimen comprising intravenous administration of one or more doses of a fusion protein comprising a B7-H4 polypeptide comprising the IgV domain of SEQ ID NO: 63 or SEQ ID NO: 64
1. A method for reducing inflammation in a human subject, the method comprising treating the subject according to a dosage regimen comprising intravenous administration of one or more doses of a fusion protein comprising a B7-H4 polypeptide comprising the IgV domain of SEQ ID NO: 63 or SEQ ID NO: 64 fused to a second polypeptide or fused to a linker peptide fused to a second polypeptide, wherein the dosage regimen is effective to achieve at least a 1.0 μg/ml concentration of the fusion protein in the subject post administration, and wherein the dosage regimen increases the ratio of regulatory T cells (Tregs) relative to total CD4+ cells and reduces inflammation in the subject for at least a week post administration. 2. The method of claim 1, wherein the dosage regimen comprises at least one dose of 3 mg/kg to 20 mg/kg of the fusion protein. 3. The method of claim 1, wherein the dosage regimen comprises intravenous administration of doses of the fusion protein to the subject at least two days apart and within two weeks. 4. The method of claim 1, wherein the dosage regimen comprises intravenous administration of doses of the fusion protein to the subject at least two days apart and within one week. 5. The method of claim 1, wherein the dosage regimen comprises intravenous administration of two or more doses of the fusion protein to the subject at least two days apart and within one week. 6. The method of claim 1, wherein the dosage regimen is effective to reduce inflammation in the subject for at least 10 days. 7. The method of claim 1, wherein the dosage regimen is effective to reduce inflammation in the subject for at least two weeks. 8. The method of claim 1, wherein the dosage regimen is effective to reduce inflammation in the subject for at least three weeks. 9. The method of claim 1, wherein the dosage regimen is effective to increase the ratio of Tregs relative to total CD4+ cells at a site of inflammation, in the draining lymph nodes, in the spleen, in the central nervous system, or combinations thereof. 10. The method of claim 1, wherein the dosage regimen is effective to reduce the ratio of effector or memory T cells relative to total CD4+ cells in the subject. 11. The method of claim 10, wherein the dosage regimen is effective to reduce the ratio of effector or memory T cells relative to total CD4+ cells at a site of inflammation in the subject. 12. The method of claim 1, wherein the second polypeptide comprises the hinge, CH2 and CH3 regions of an immunoglobulin. 13. The method of claim 12, wherein the immunoglobulin is a human IgG1. 14. The method of claim 1, wherein the subject has a disease selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus, alopecia areata, ankylosing spondylitis, antiphospholipid syndrome, autoimmune Addison's disease, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease, autoimmune lymphoproliferative syndrome (alps), autoimmune thrombocytopenic purpura (ATP), Behcet's disease, bullous pemphigoid, cardiomyopathy, celiac sprue-dermatitis, chronic fatigue syndrome immune deficiency syndrome (CFIDS), chronic inflammatory demyelinating polyneuropathy, cicatrical pemphigoid, cold agglutinin disease, Crest syndrome, Crohn's disease, Degos disease, dermatomyositis, dermatomyositis-juvenile, discoid lupus, essential mixed cryoglobulinemia, fibromyalgia-fibromyositis, Grave's disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, idiopathic pulmonary fibrosis, idiopathic thrombocytopenia purpura (ITP), IgA nephropathy, insulin dependent diabetes (Type I), juvenile arthritis, Meniere's disease, mixed connective tissue disease, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, pernicious anemia, polyarteritis nodosa, polychondritis, polyglandular syndromes, polymyalgia rheumatica, polymyositis and dermatomyositis, primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, Raynaud's phenomenon, Reiter's syndrome, rheumatic fever, sarcoidosis, scleroderma, Sjogren's syndrome, stiff-man syndrome, Takayasu arteritis, temporal arteritis/giant cell arteritis, ulcerative colitis, uveitis, vasculitis, vitiligo, and Wegener's granulomatosis. 15. The method claim 14, wherein the disease is Sjogren's syndrome, multiple sclerosis, rheumatoid arthritis, Crohn's disease, or myasthenia gravis. 16. The method of claim 15, wherein the disease is rheumatoid arthritis. 17. A method for reducing inflammation in a human subject, the method comprising treating the subject according to a dosage regimen comprising intravenous administration of one or more doses of a fusion protein comprising the amino acid sequence of SEQ ID NO: 130, wherein the dosage regimen is effective to achieve at least a 1.0 μg/ml concentration of the fusion protein in the subject post administration, and wherein the dosage regimen increases the ratio of regulatory T cells (Tregs) relative to total CD4+ cells and reduces inflammation in the subject for at least a week post administration. 18. The method of claim 17, wherein the dosage regimen comprises at least one dose of 3 mg/kg to 20 mg/kg of the fusion protein. 19. The method of claim 17, wherein the dosage regimen comprises intravenous administration of doses of the fusion protein to the subject at least two days apart and within two weeks. 20. The method of claim 17, wherein the dosage regimen comprises intravenous administration of doses of the fusion protein to the subject at least two days apart and within one week. 21. The method of claim 17, wherein the dosage regimen comprises intravenous administration of two or more doses of the fusion protein to the subject at least two days apart and within one week. 22. The method of claim 17, wherein the dosage regimen is effective to reduce inflammation in the subject for at least 10 days. 23. The method of claim 17, wherein the dosage regimen is effective to reduce inflammation in the subject for at least two weeks. 24. The method of claim 17, wherein the dosage regimen is effective to reduce inflammation in the subject for at least three weeks. 25. The method of claim 17, wherein the dosage regimen is effective to increase the ratio of Tregs relative to total CD4+ cells at a site of inflammation, in the draining lymph nodes, in the spleen, in the central nervous system, or combinations thereof. 26. The method of claim 17, wherein the dosage regimen is effective to reduce the ratio of effector or memory T cells relative to total CD4+ cells in the subject. 27. The method of claim 26, wherein the dosage regimen is effective to reduce the ratio of effector or memory T cells relative to total CD4+ cells at a site of inflammation in the subject. 28. The method of claim 17, wherein the subject has a disease selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus, alopecia areata, ankylosing spondylitis, antiphospholipid syndrome, autoimmune Addison's disease, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease, autoimmune lymphoproliferative syndrome (alps), autoimmune thrombocytopenic purpura (ATP), Behcet's disease, bullous pemphigoid, cardiomyopathy, celiac sprue-dermatitis, chronic fatigue syndrome immune deficiency, syndrome (CFIDS), chronic inflammatory demyelinating polyneuropathy, cicatrical pemphigoid, cold agglutinin disease, Crest syndrome, Crohn's disease, Degos disease, dermatomyositis, dermatomyositis-juvenile, discoid lupus, essential mixed cryoglobulinemia, fibromyalgia-fibromyositis, Grave's disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, idiopathic pulmonary fibrosis, idiopathic thrombocytopenia purpura (ITP), IgA nephropathy, insulin dependent diabetes (Type I), juvenile arthritis, Meniere's disease, mixed connective tissue disease, multiple sclerosis, myasthenia gravis, pemphigus vulgaris, pernicious anemia, polyarteritis nodosa, polychondritis, polyglandular syndromes, polymyalgia rheumatica, polymyositis and dermatomyositis, primary agammaglobulinemia, primary biliary cirrhosis, psoriasis, Raynaud's phenomenon, Reiter's syndrome, rheumatic fever, sarcoidosis, scleroderma, Sjogren's syndrome, stiff-man syndrome, Takayasu arteritis, temporal arteritis/giant cell arteritis, ulcerative colitis, uveitis, vasculitis, vitiligo, and Wegener's granulomatosis. 29. The method claim 28, wherein the disease is Sjogren's syndrome, multiple sclerosis, rheumatoid arthritis, Crohn's disease, or myasthenia gravis. 30. The method of claim 29, wherein the disease is rheumatoid arthritis. 31. A method for treating an autoimmune disorder in a human subject, the method comprising treating the subject according to a dosage regimen comprising intravenous administration of one or more doses of a fusion protein comprising a B7-H4 polypeptide comprising the IgV domain of SEQ ID NO: 63 or SEQ ID NO: 64 fused to a second polypeptide or fused to a linker peptide fused to a second polypeptide, wherein the dosage regimen is effective to achieve at least a 1.0 μg/ml concentration of the fusion protein in the subject post administration, and wherein the dosage regimen increases the ratio of regulatory T cells (Tregs) relative to total CD4+ cells and reduces inflammation in the subject for at least a week post administration. 32. The method of claim 31, wherein the dosage regimen comprises at least one dose of 3 mg/kg to 20 mg/kg of the fusion protein. 33. The method of claim 31, wherein the dosage regimen comprises intravenous administration of doses of the fusion protein to the subject at least two days apart and within two weeks. 34. The method of claim 31, wherein the dosage regimen comprises intravenous administration of doses of the fusion protein to the subject at least two days apart and within one week. 35. The method of claim 31, wherein the dosage regimen comprises intravenous administration of two or more doses of the fusion protein to the subject at least two days apart and within one week. 36. The method of claim 31, wherein the dosage regimen is effective to reduce inflammation in the subject for at least 10 days. 37. The method of claim 31, wherein the dosage regimen is effective to reduce inflammation in the subject for at least two weeks. 38. The method of claim 31, wherein the dosage regimen is effective to reduce inflammation in the subject for at least three weeks. 39. The method of claim 31, wherein the dosage regimen is effective to increase the ratio of Tregs relative to total CD4+ cells at a site of inflammation, in the draining lymph nodes, in the spleen, in the central nervous system, or combinations thereof. 40. The method of claim 31, wherein the dosage regimen is effective to reduce the ratio of effector or memory T cells relative to total CD4+ cells in the subject. 41. The method of claim 40, wherein the dosage regimen is effective to reduce the ratio of effector or memory T cells relative to total CD4+ cells at a site of inflammation in the subject. 42. The method of claim 31, wherein the second polypeptide comprises the hinge, CH2 and CH3 regions of an immunoglobulin. 43. The method of claim 42, wherein the immunoglobulin is a human IgG1. 44. A method for treating an autoimmune disorder in a human subject, the method comprising treating the subject according to a dosage regimen comprising intravenous administration of one or more doses of a fusion protein comprising the amino acid sequence of SEQ ID NO: 130, wherein the dosage regimen is effective to achieve at least a 1.0 μg/ml concentration of the fusion protein in the subject post administration, and wherein the dosage regimen increases the ratio of regulatory T cells (Tregs) relative to total CD4+ cells and reduces inflammation in the subject for at least a week post administration. 45. The method of claim 44, wherein the dosage regimen comprises at least one dose of 3 mg/kg to 20 mg/kg of the fusion protein. 46. The method of claim 44, wherein the dosage regimen comprises intravenous administration of doses of the fusion protein to the subject at least two days apart and within two weeks. 47. The method of claim 44, wherein the dosage regimen comprises intravenous administration of doses of the fusion protein to the subject at least two days apart and within one week. 48. The method of claim 44, wherein the dosage regimen comprises intravenous administration of two or more doses of the fusion protein to the subject at least two days apart and within one week. 49. The method of claim 44, wherein the dosage regimen is effective to reduce inflammation in the subject for at least 10 days. 50. The method of claim 44, wherein the dosage regimen is effective to reduce inflammation in the subject for at least two weeks. 51. The method of claim 44, wherein the dosage regimen is effective to reduce inflammation in the subject for at least three weeks. 52. The method of claim 44, wherein the dosage regimen is effective to increase the ratio of Tregs relative to total CD4+ cells at a site of inflammation, in the draining lymph nodes, in the spleen, in the central nervous system, or combinations thereof. 53. The method of claim 44, wherein the dosage regimen is effective to reduce the ratio of effector or memory T cells relative to total CD4+ cells in the subject. 54. The method of claim 53, wherein the dosage regimen is effective to reduce the ratio of effector or memory T cells relative to total CD4+ cells at a site of inflammation in the subject.
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Summerton James E. (Corvallis OR) Weller Dwight D. (Corvallis OR) Stirchak Eugene P. (Corvallis OR), Alpha-morpholino ribonucleoside derivatives and polymers thereof.
Failli Amedeo A. (Princeton Junction NJ) Bleyman Oleg I. (Holland PA) Kao Wenling (Paoli PA) Abou-Gharbia Magid A. (Glen Mills PA), Carbamates of rapamycin.
Skotnicki Jerauld S. (Allentown NJ) Palmer Yvette L. (Newtown PA) Kao Wenling (Paoli PA) Abou-Gharbia Magid A. (Glen Mills PA), Carbamates of rapamycin.
Skotnicki Jerauld S. (Allentown NJ) Palmer Yvette L. (Newtown PA) Kao Wenling (Paoli PA) Abou-Gharbia Magid A. (Glen Mills PA), Carbamates of rapamycin.
Mitcham,Jennifer L.; King,Gordon E.; Algate,Paul A.; Fling,Steven P.; Retter,Marc W.; Fanger,Gary R.; Reed,Steven G., Compositions and methods for the therapy and diagnosis of ovarian cancer.
Herzig Yaacov,ILX ; Sterling Jeff,ILX ; Veinberg Alex,ILX ; Sklarz Benjamin,ILX ; Lidor Ramy,ILX ; Bahar Eliezer,ILX, Compositions containing and methods of using 1-aminoindan and derivatives thereof and process for preparing optically a.
Ladner Robert C. (3827 Green Valley Iamsville MD 21754), Computer based system and method for determining and displaying possible chemical structures for converting double- or m.
Chen,Lieping; Strome,Scott E., Detection of antibodies specific for B7-H1 in subjects with diseases or pathological conditions mediated by activated T cells.
Queen Cary L. (Los Altos CA) Co Man Sung (Cupertino CA) Schneider William P. (Mountain View CA) Landolfi Nicholas F. (Milpitas CA) Coelingh Kathleen L. (San Francisco CA) Selick Harold E. (Belmont CA, Humanized immunoglobulins.
Woodle Martin C. (Menlo Park CA) Martin Francis J. (San Francisco CA) Yau-Young Annie (Los Altos CA) Redemann Carl T. (Walnut Creek CA), Liposomes with enhanced circulation time.
Helliwell, Christopher A.; Wesley, Susan V.; Waterhouse, Peter M., Methods and means for producing efficient silencing construct using recombinational cloning.
Johnson Kevin Stuart,GBX ; Winter Gregory Paul,GBX ; Griffiths Andrew David,GBX ; Smith Andrew John Hammond,GBX ; Waterhouse Peter Michael,AUX, Methods for producing members of specific binding pairs.
Winter Gregory Paul,GBX ; Johnson Kevin Stuart,GBX ; Griffiths Andrew David,GBX ; Smith Andrew John Hammond,GBX, Methods for producing members of specific binding pairs.
Winter Gregory Paul,GBX ; Johnson Kevin Stuart,GBX ; Griffiths Andrew David,GBX ; Smith Andrew John Hammond,GBX, Methods for producing members of specific binding pairs.
Matteucci Mark (Burlingame CA) Jones Robert J. (Daly City CA) Munger John (San Francisco CA), Modified internucleoside linkages having one nitrogen and two carbon atoms.
Holliger Kaspar-Philipp,GBX ; Griffiths Andrew David,GBX ; Hoogenboom Hendricus Renerus Jacobus Matheus,BEX ; Malmqvist Magnus,SEX ; Marks James David ; McGuinness Brian Timothy,GBX ; Pope Anthony Ri, Multivalent and multispecific binding proteins, their manufacture and use.
Ts\o Paul O. P. (2117 Folkstone Rd. Lutherville MD 21093) Miller Paul S. (225 Hopkins Rd. Baltimore MD 21212), Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof.
Queen Cary L. (Los Altos CA) Schneider William P. (Mountain View CA) Selick Harold E. (Belmont CA), Polynucleotides encoding improved humanized immunoglobulins.
Hoogenboom Hendricus R. J. M. (Cambridge GBX) Baier Michael (Frankfurt DEX) Jespers Laurent S. A. T. (Tervuren BEX) Winter Gregory P. (Cambridge GBX), Production of chimeric antibodies - a combinatorial approach.
Fell ; Jr. H. Perry (Redmond WA) Folger-Bruce Kim R. (Seattle WA) Yarnold Susan M. (Seattle WA), Production of chimeric antibodies by homologous recombination.
Platz Robert M. (Half Moon Bay CA) Winters Mark A. (Mountain View CA) Pitt Colin G. (Thousand Oaks CA), Pulmonary administration of granulocyte colony stimulating factor.
Waranis Robert P. (Chazy NY) Harrison Maureen M. (St. Albans VT) Leonard Thomas W. (Plattsburgh NY) Enever Robin P. (Rouses Point NY), Rapamycin formulation for IV injection.
Cabilly Shmuel (Monrovia CA) Heyneker Herbert L. (Burlingame CA) Holmes William E. (Pacifica CA) Riggs Arthur D. (La Verne CA) Wetzel Ronald B. (San Francisco CA), Recombinant immunoglobin preparations.
Moretta, Alessandro; Castriconi, Roberta; Bottino, Christina; Moretta, Lorenzo, Therapeutic and diagnostic methods and compositions targeting 4Ig-B7-H3 and its counterpart NK cell receptor.
Deboer Herman A.,NLX ; Strijker Rein,NLX ; Heyneker Herbert L. ; Platenburg Gerard,NLX ; Lee Sang He,NLX ; Pieper Frank,NLX ; Krimpenfort Paul J. A.,NLX, Transgenic bovine.
Lonberg Nils (San Francisco CA) Kay Robert M. (San Francisco CA), Transgenic non-human animals capable of producing heterologous antibodies of various isotypes.
Lonberg Nils (San Francisco CA) Kay Robert M. (San Francisco CA), Transgenic non-human animals capable of producing heterologous antibodies of various isotypes.
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