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Treatment for inflammatory bowel diseaseRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Radionuclide Or Intended Radionuclide Containing; Adjuvant Or Carrier Compositions; Intermediate Or Preparatory Compositions, In An Organic Compound, Attached To Peptide Or Protein Of 2+ Amino Acid Units (e.g., Dipeptide, Folate, Fibrinogen, Transferrin, Sp. Enzymes); Derivative ThereofTreatment for inflammatory bowel disease description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070253902, Treatment for inflammatory bowel disease. Brief Patent Description - Full Patent Description - Patent Application Claims
RELATED APPLICATIONS [0001] This application is a continuation application of U.S. patent application Ser. No. 10/252,978, filed on Sep. 23, 2002, which is a continuation application of U.S. patent application Ser. No. 09/157,452, filed on Sep. 21, 1998, now U.S. Pat. No. 6,482,409, which is a continuation application of U.S. patent application Ser. No. 08/950,660, filed on Oct. 15, 1997, now U.S. Pat. No. 5,932,214, which is a file wrapper continuation application of U.S. patent application Ser. No. 08/456,124, filed on May 31, 1995, now abandoned, which is a continuation-in-part application U.S. patent application Ser. No. 08/373,857, filed on Jan. 18, 1995, now abandoned, which is a continuation-in-part application of U.S. patent application Ser. No. 08/284,603, filed on Aug. 11, 1994, now abandoned, and of International Patent Application No. PCT/US93/00924, filed on Feb. 2, 1993, which is a continuation-in-part application of U.S. patent application Ser. No. 07/835,139, filed Feb. 12, 1992, now abandoned. The contents of the prior applications are hereby incorporated by reference in their entirety for all purposes. FIELD OF THE INVENTION [0002] The present invention relates to a treatment for inflammatory bowel disease (IBD). More particularly, this invention relates to the use of antibodies recognizing the integrin VLA-4 (very late antigen-4) in the treatment of IBD. BACKGROUND OF THE INVENTION [0003] Inflammatory bowel disease, or IBD, is a collective term encompassing ulcerative colitis and Crohn's disease (ileitis), which are chronic inflammatory disorders of the gastrointestinal tract. Ulcerative colitis is confined to the large intestine (colon) and rectum, and involves only the inner lining of the intestinal wall. Crohn's disease may affect any section of the gastrointestinal tract (i.e., mouth, esophagus, stomach, small intestine, large intestine, rectum and anus) and may involve all layers of the intestinal wall. Both diseases are characterized by abdominal pain and cramping, diarrhea, rectal bleeding and fever. The symptoms of these diseases are usually progressive, and sufferers typically experience periods of remission followed by severe flareups. [0004] IBD affects an estimated two million people in the United States alone. Although IBD is not considered a fatal illness, prolonged disease can lead to severe malnutrition affecting growth or to the formation of abscesses or intestinal scar tissue, leading in turn to infection or bowel obstruction. [0005] IBD has no cure, and the exact causes of IBD are not yet understood. Conventional treatments for IBD have involved anti-inflammatory drugs, immunosuppressive drugs and surgery. Sulfasalazine and related drugs having the bioactive 5-amino-salicylic acid (5-ASA) moiety are widely used to control moderate IBD symptoms and to maintain remission. Severe inflammation is often treated with powerful corticosteroids and sometimes ACTH or with immunosuppressants such as 6-mercaptopurine and azathioprine. The most common surgical treatments for severe chronic IBD are intestinal resections and, ultimately, colectomy, which is a complete cure only for ulcerative colitis. [0006] Severe side effects are associated with the drugs commonly prescribed for IBD, including nausea, dizziness, changes in blood chemistry (including anemia and leukopenia), skin rashes and drug dependence; and the surgical treatments are radical procedures that often profoundly alter the everyday life of the patient. Accordingly, there is a great need for treatments for IBD that are effective yet less severe in their side effects and are less invasive of the IBD sufferer's body and quality of life. [0007] The search for the causes of IBD and more effective treatments has led several investigators to study diseased and normal tissue on a cellular level. This has led to observations of variations in the normal content of intestinal mucin (Podolsky, 1988 [1]) and to the observation of colonic glycoproteins that emerge only in diseased tissue (Podolsky and Fournier, 1988a [2], 1988b [3]). Researchers have observed that the cell adhesion molecule ICAM-1 is expressed at elevated levels in IBD tissue (Malizia et al., 1991 [4]). This molecule is thought to mediate leukocyte recruitment to sites of inflammation through adhesion to leukocyte surface ligands, i.e., LFA-1 (CD11a/CD18 complex) on all leukocytes and Mac-1 (CD11b/CD18) on phagocytes. (See, e.g., Springer, 1990 [5].) Because flareups of IBD are often accompanied by increased concentrations of neutrophils and lymphocytes in the intestinal submucosa, blocking of interactions between endothelial cell receptors (such as ICAM-1) and their leukocyte ligands (such as LFA-1, Mac-1) has been proposed as a treatment for IBD. [0008] Another cell adhesion molecule, VCAM-1 (vascular cell adhesion molecule-1) is expressed on inflamed endothelium and has been shown to recognize the .alpha..sub.4.beta..sub.1 integrin, VLA-4, expressed on the surface of all leukocytes except neutrophils (Springer, 1990 [5]). VCAM-1 also has been found to be expressed constitutively in noninflamed tissue, including Peyer's patch follicular dendritic cells (Freedman et al., 1990 [6]; Rice et al., 1991 [7]). Additionally, besides mediating cell adhesion events, VCAM-1 also has recently been determined to play a costimulatory role, through VLA-4, in T cell activation (Burkly et al., 1991 [8]; Damle and Arrufo, 1991 [9]; van Seventer et al., 1991 [10]). Accordingly, further study of VCAM-1 has been taken up to investigate whether it plays a role as a regulator of the immune response as well as a mediator of adhesion in vivo. [0009] It has now been surprisingly discovered that administering anti-VLA-4 antibody significantly reduces acute inflammation in a primate model for IBD. Cotton top tamarins suffering from a spontaneous intestinal inflammation comparable to ulcerative colitis in humans that were treated with an anti-VLA-4 antibody (HP1/2) showed significant reduction in inflammation of biopsied intestinal tissue. SUMMARY OF THE INVENTION [0010] Accordingly, the present invention provides novel methods for the treatment of IBD and further provides new pharmaceutical compositions useful in the treatment of IBD. In particular, the present invention provides a method comprising the step of administering to an IBD sufferer a VLA-4 blocking agent, e.g., an anti-VLA-4 antibody, such as antibody HP1/2 Also contemplated is the use of analogous antibodies, antibody fragments, soluble proteins and small molecules that mimic the action of anti-VLA-4 antibodies in the treatment of IBD. DETAILED DESCRIPTION OF THE DRAWINGS [0011] FIG. 1 is a schematic depicting structure of VCAM 2D-IgG fusion protein described in Example V. VCAM 2D-IgG is a soluble form of the ligand for VLA4 (VCAM1) and consists of the two N-terminal domains of VCAM 1 fused to the human IgG1 heavy chain constant region sequences (Hinges, C.sub.H2 and C.sub.H3). [0012] FIG. 2 is graph depicting VCAM-IgG inhibitory dose response after single intraperitoneal doses in mouse contact hypersensitivity. VCAM-IgG tested over a dose range of 1.25 to 20 mg/kg (25-400 .mu.g/mouse) maximally inhibited the mouse ear swelling response about 4/5 as well as the PS/2 antibody. Maximal inhibition occurred at the 10 mg/kg dose. The ED50 was about 2.5 mg/kg, i.p. (50 .mu.g/mouse). [0013] FIG. 3 is a graph depicting inhibition of the mouse ear swelling response by VCAM-IgG in mouse contact hypersensitivity. In a confirmation study, VCAM-IgG tested at 20 mg/kg i.p. (400 .mu.g/mouse) maximally inhibited the mouse ear swelling response as effectively as the PS/2 8 mg/kg i.v. antibody dose. [0014] FIG. 4 is a graph depicting the effect of VCAM 2D-IgG fusion protein and controls on prevention of diabetes after adoptive transfer of spleen cells; the frequency of recipients which became diabetic and day of disease onset are shown for transfer of 2.times.10.sup.7 splenocytes from diabetic (D) NOD donors with an irrelevant rat LFA-3Ig fusion protein treatment (closed squares), and with VCAM 2D-IgG treatment (open circles) or of recipients which received PBS alone without cells transferred (closed triangles); the splenocytes were transferred with VCAM 2D-IgG or rat LFA-3Ig, and then VCAM 2D-IgG or rat LFA-3Ig was injected every other day through day 17 post-transfer (n=5 for all groups). [0015] FIG. 5 is a graph depicting the effect of VCAM-Ig (30 mg, aerosol given 30 min before antigen challenge) on airway hyperresponsiveness in dual responder sheep. This dose resulted in significant but partial inhibition of LPR, but no effect on AHR. [0016] FIG. 6 is a graph depicting the effect of VCAM-Ig (60 mg, aerosol given 30 min before antigen challenge) on airway hyperresponsiveness in dual responder sheep. This dose resulted in significant but partial inhibition of LPR, and inhibition of AHR. [0017] FIG. 7 is a graph depicting the effect of VCAM-Ig (30 mgs, aerosol given 30 min. before antigen challenge and 8 h. after challenge) on airway hyperresponsiveness in dual responder sheep. This dose resulted in complete inhibition of LPR, but no inhibition of AHR. [0018] FIG. 8 is a graph depicting the effect of VCAM-Ig (15 mgs, aerosol given 2, 8 and 24 h. after antigen challenge) on airway hyperresponsiveness in dual responder sheep. This dose resulted in a significant but partial inhibition of LPR, and inhibition of AHR. [0019] FIG. 9 is a graph depicting the effect of VCAM-Ig (30 mgs, aerosol given 2, and 24 h. after antigen challenge) on airway hyperresponsiveness in dual responder sheep. This optimal dose resulted in complete inhibition of both LPR and AHR. Continue reading about Treatment for inflammatory bowel disease... Full patent description for Treatment for inflammatory bowel disease Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Treatment for inflammatory bowel disease patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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