METHODS OF INHIBITING INFLAMMATION AND INFLAMMATORY DISEASES USING Gal-3BP (BTBD17B, LGALS3BP, GALECTIN-3 BINDING PROTEIN, MAC-2 BINDING PROTEIN)
원문보기
IPC분류정보
국가/구분
United States(US) Patent
공개
국제특허분류(IPC7판)
A61K-038/17
A61K-045/06
C07K-014/435
출원번호
US-0627839
(2012-09-26)
공개번호
US-0095127
(2013-04-18)
발명자
/ 주소
LA JOLLA INSTITUTE FOR ALLERGY AND IMMU
출원인 / 주소
LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY
인용정보
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초록▼
The invention provides Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptides, Gal-3BP compositions, and methods of use, and uses, for example, in treatment, diagnostic, detection and prognostic methods, such as treatment of an undesirable or aberrant immune response, immune disorder, inflammato
The invention provides Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptides, Gal-3BP compositions, and methods of use, and uses, for example, in treatment, diagnostic, detection and prognostic methods, such as treatment of an undesirable or aberrant immune response, immune disorder, inflammatory response, or inflammation, and treatment of an autoimmune response, disorder or disease.
대표청구항▼
1. A method of decreasing, reducing, inhibiting, suppressing, limiting or controlling an undesirable or aberrant immune response, immune disorder, inflammatory response, inflammation or an autoimmune response, disorder or disease in a subject, comprising administering a Galectin-3 binding protein (G
1. A method of decreasing, reducing, inhibiting, suppressing, limiting or controlling an undesirable or aberrant immune response, immune disorder, inflammatory response, inflammation or an autoimmune response, disorder or disease in a subject, comprising administering a Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide or fragment thereof to a subject in an amount to decrease, reduce, inhibit, suppress, limit or control the undesirable or aberrant immune response, immune disorder, inflammatory response, inflammation or autoimmune response, disorder or disease in the subject, wherein the subject has not been diagnosed for an adverse cardiovascular event or cardiovascular disease. 2. (canceled) 3. The method of claim 1, wherein the treatment decreases, reduces, inhibits, suppresses, limits or controls an adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response, or inflammation, or an adverse symptom of the autoimmune response, disorder or disease. 4.-6. (canceled) 7. The method of claim 1, wherein the Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide or fragment thereof stimulates, promotes, increases or induces interleukin-2 (IL-2) production by or secretion from macrophages or dendritic cells. 8. The method of claim 3, wherein the interleukin-2 (IL-2) stimulates, promotes, increases or induces survival, proliferation or differentiation of regulatory T cells (T regs). 9. The method of claim 1, wherein the Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide or fragment thereof stimulates, promotes, increases or induces nuclear factor of activated T cells (NFAT) activation. 10. The method of claim 5, wherein the NFAT activation is indicated by stimulated, promoted, increased or induced macrophage microRNA expression, has-miR-21, has-miR-23b, has-miR-24, has-miR-27a or has-miR-125a-5p. 11. The method of claim 1, wherein the Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide or fragment thereof decreases, reduces or inhibits TNF-alpha or interleukin-6 (IL-6) production or secretion by splenocytes or macrophages. 12.-13. (canceled) 14. The method of claim 1, wherein the subject has or has had an adverse symptom of the undesirable or aberrant immune response, immune disorder, inflammatory response, inflammation, or autoimmune response, disorder or disease, or has an existing undesirable or aberrant immune response, immune disorder, inflammatory response, inflammation, or autoimmune response, disorder or disease. 15. (canceled) 16. The method of claim 1, wherein the subject is in need of treatment for an undesirable or aberrant immune response, immune disorder, inflammatory response, inflammation, or autoimmune response, disorder or disease, or is at risk of an undesirable or aberrant immune response, immune disorder, inflammatory response, inflammation, or autoimmune response, disorder or disease. 17.-18. (canceled) 19. The method of claim 1, wherein the Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide comprises a polypeptide fragment of full length Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide. 20. The method of claim 1, wherein the Gal-3BP polypeptide is human, Pan troglodyte, Canis lupus familiaris, Bos Taurus, Mus musculus or Rattus norvegicus, SEQ ID NOs: 1-6, respectively. 21. (canceled) 22. The method of claim 1, wherein the Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide comprises full length or a subsequence of: 10 20 30 40 50 60MTPPRLFWVW LLVAGTQGVN DGDMRLADGG ATNQGRVEIF YRGQWGTVCD NLWDLTDASV 70 80 90 100 110 120VCRALGFENA TQALGRAAFG QGSGPIMLDE VQCTGTEASL ADCKSLGWLK SNCRHERDAG 130 140 150 160 170 180VVCTNETRST HTLDLSRELS EALGQIFDSQ RGCDLSISVN VQGEDALGFC GHTVILTANL 190 200 210 220 230 240EAQALWKEPG SNVTMSVDAE CVPMVRDLLR YFYSRRIDIT LSSVKCFHKL ASAYGARQLQ 250 260 270 280 290 300GYCASLFAIL LPQDPSFQMP LDLYAYAVAT GDALLEKLCL QFLAWNFEAL TQAEAWPSVP 310 320 330 340 350 360TDLLQLLLPR SDLAVPSELA LLKAVDTWSW GERASHEEVE GLVEKIRFPM MLPEELFELQ 370 380 390 400 410 420FNLSLYWSHE ALFQKKTLQA LEFHTVPFQL LARYKGLNLT EDTYKPRIYT SPTWSAFVTD 430 440 450 460 470 480SSWSARKSQL VYQSRRGPLV KYSSDYFQAP SDYRYYPYQS FQTPQHPSFL FQDKRVSWSL 490 500 510 520 530 540VYLPTIQSCW NYGFSCSSDE LPVLGLTKSG GSDRTIAYEN KALMLCEGLF VADVTDFEGW 550 560 570 580KAAIPSALDT NSSKSTSSFP CPAGHFNGFR TVIRPFYLTN SSGVD 23. The method of claim 12, wherein the Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide subsequence is residues 24-124 (SRCR domain); residues 153-221 (BTB domain); or residues 260-360 (BACK domain). 24. The method of claim 1, wherein the Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide comprises a fusion polypeptide, or a chimeric polypeptide. 25. The method of claim 14, wherein the chimeric polypeptide comprises a Galectin-3 binding protein (Gal-3BP, BTBD17B)/Immunoglobulin fusion polypeptide. 26.-33. (canceled) 34. The method of claim 1, wherein the immune disorder, inflammatory response, inflammation, autoimmune response, disorder or disease, comprises rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis, diabetes mellitus, multiple sclerosis, encephalomyelitis, myasthenia gravis, systemic lupus erythematosus (SLE), autoimmune thyroiditis, atopic dermatitis, eczematous dermatitis, psoriasis, Sjögren's Syndrome, Crohn's disease, aphthous ulcer, iritis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, inflammatory bowel disease (IBD), cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, erythema nodosum leprosum, autoimmune uveitis, allergic encephalomyelitis, acute necrotizing hemorrhagic encephalopathy, idiopathic bilateral progressive sensorineural hearing loss, aplastic anemia, pure red cell anemia, idiopathic thrombocytopenia, polychondritis, Wegener's granulomatosis, chronic active hepatitis, Stevens-Johnson syndrome, idiopathic sprue, lichen planus, Graves' disease, sarcoidosis, primary biliary cirrhosis, uveitis posterior, interstitial lung fibrosis, Hashimoto's thyroiditis, autoimmune polyglandular syndrome, insulin-dependent diabetes mellitus, insulin-resistant diabetes mellitus, immune-mediated infertility, autoimmune Addison's disease, pemphigus vulgaris, pemphigus foliaceus, dermatitis herpetiformis, autoimmune alopecia, vitiligo, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, pernicious anemia, Guillain-Barre syndrome, stiff-man syndrome, acute rheumatic fever, sympathetic ophthalmia, Goodpasture's syndrome, systemic necrotizing vasculitis, antiphospholipid syndrome or an allergy, Behcet's disease, severe combined immunodeficiency (SCID), recombinase activating gene (RAG 1/2) deficiency, adenosine deaminase (ADA) deficiency, interleukin receptor common γ chain (γc) deficiency, Janus-associated kinase 3 (JAK3) deficiency and reticular dysgenesis; primary T cell immunodeficiency such as DiGeorge syndrome, Nude syndrome, T cell receptor deficiency, MHC class II deficiency, TAP-2 deficiency (MHC class I deficiency), ZAP70 tyrosine kinase deficiency and purine nucleotide phosphorylase (PNP) deficiency, antibody deficiencies, X-linked agammaglobulinemia (Bruton's tyrosine kinase deficiency), autosomal recessive agammaglobulinemia, Mu heavy chain deficiency, surrogate light chain (γ5/14.1) deficiency, Hyper-IgM syndrome: X-linked (CD40 ligand deficiency) or non-X-linked, Ig heavy chain gene deletion, IgA deficiency, deficiency of IgG subclasses (with or without IgA deficiency), common variable immunodeficiency (CVID), antibody deficiency with normal immunoglobulins; transient hypogammaglobulinemia of infancy, interferon γ receptor (IFNGR1, IFNGR2) deficiency, interleukin 12 or interleukin 12 receptor deficiency, immunodeficiency with thymoma, Wiskott-Aldrich syndrome (WAS protein deficiency), ataxia telangiectasia (ATM deficiency), X-linked lymphoproliferative syndrome (SH2D1A/SAP deficiency), or hyper IgE syndrome. 35.-37. (canceled) 38. The method of claim 1, wherein the subject is not in need of treatment or therapy for artherosclerotic plaque formation, elevated blood cholesterol or a cardiovascular disease, or has not been diagnosed for cancer, has not been treated for cancer, or is in remission from cancer. 39. (canceled) 40. The method of claim 1, wherein the subject is a mammal. 41. (canceled) 42. A pharmaceutical composition comprising Galectin-3 binding protein (Gal-BP, BTBD17B) and an anti-inflammatory drug or agent. 43. A method of stimulating, promoting, increasing or inducing interleukin-2 (IL-2) production by or secretion from macrophages or dendritic cells or decreasing, reducing or inhibiting TNF-alpha or IL-6 production or secretion by splenocytes or macrophages, comprising administering Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide or fragment thereof to a subject in an amount that stimulates, promotes, increases or induces interleukin-2 (IL-2) production by or secretion from macrophages or dendritic cells or decreases, reduces or inhibits TNF-alpha or IL-6 production or secretion by splenocytes or macrophages, wherein the subject has not been diagnosed for an adverse cardiovascular event or cardiovascular disease. 44. A method of decreasing, reducing or inhibiting TNF-alpha or IL-6 production or secretion by splenocytes or macrophages, comprising administering Galectin-3 binding protein (Gal-3BP, BTBD17B) polypeptide or fragment thereof to a subject in an amount that decreases, reduces or inhibits TNF-alpha or IL-6 production or secretion by splenocytes or macrophages, wherein the subject has not been diagnosed for an adverse cardiovascular event or cardiovascular disease.
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