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Treatment for inflammatory bowel disease

a technology for inflammatory bowel disease and treatment, which is applied in the direction of anti-immunoglobulin, therapy, peptide/protein ingredients, etc., can solve the problems of infection or bowel obstruction, ibd has no cure, and ibd is not yet understood

Inactive Publication Date: 2007-11-01
BIOGEN MA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

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.
IBD has no cure, and the exact causes of IBD are not yet understood.
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.

Method used

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  • Treatment for inflammatory bowel disease
  • Treatment for inflammatory bowel disease
  • Treatment for inflammatory bowel disease

Examples

Experimental program
Comparison scheme
Effect test

example i

VCAM1 Expression in the Colon

[0048] Experiments were performed to determine whether active IBD involved the expression of endothelial cell surface proteins involved in leukocyte adhesion. Expression of VCAM-1 in colon tissue of IBD sufferers and normal or uninvolved colon tissue controls was evaluated. Human colonoscopic biopsy tissue samples were obtained, with informed consent, and prepared as frozen sections by mounting in OCT compound (TissueTek) and quick freezing in isopentane / liquid nitrogen. The human colon samples were from normal colon, active ulcerative colitis colon (UC-active), inactive ulcerative colitis colon (UC-inactive), uninvolved ulcerative colitis colon (UC-uninvolved), active Crohn's Disease colon (CD-active), and uninvolved Crohn's Disease colon (CD-uninvolved).

[0049] Frozen sections (˜4μ) were placed on gelatin-coated slides (1% gelatin, heated at 60° C. for 1-2 min., air dried, 1% formaldehyde at room temp., air dried), air dried 30 minutes, fixed in acet...

example ii

Anti-VLA-4 Antibody Recognition of CTT White Blood Cells

[0052] An anti-VLA-4 monoclonal antibody (HP1 / 2, obtained from Biogen, Inc., Cambridge Mass.) was tested to confirm that it recognized an epitope on CTT leukocytes.

[0053] Blood samples (3 ml) from CTTs were heparinized and the CTT peripheral blood mononuclear leukocytes (PBLs) were isolated using a Ficoll-Hypaque gradient (Pharmacia) according to the manufacturer's instructions for isolation of human PBLs. CTT PBLs were examined for their ability to bind to the murine anti-human VLA-4 monoclonal antibodies HP1 / 2 and HP2 / 1 by FACS analysis using a Becton Dickenson FACStar and standard techniques (see, e.g., Lobb et al., 1991a [31]). Both monoclonal antibodies bound to CTT PBLs, indicating that both human and CTT VLA4 have similar epitopes recognized by these two antibodies.

[0054] CTT PBLs were also observed to adhere to microtiter plates coated with immobilized recombinant soluble human VCAM-1 (Biogen, Inc.), which binding w...

example iii

Cotton Top Tamarin Trials

[0055] A stock solution in sterile saline of the Anti-VLA-4 antibody, HP1 / 2 (IgG1), and a placebo control (saline only), were prepared for administration to ten cotton top tamarins (CTTs) exhibiting symptoms of spontaneous colitis (i.e., diarrhea, etc.; see, Madara et al. [18]). Five CTTs received HP1 / 2 and five received placebo, by intravenous injection. The CTTs receiving HP1 / 2 were injected with 1 mg HP1 / 2 per day (i.e., about 2 mg / kg / day, based on approximate half-kilogram weight of a CTT) for eight days (on Days 0, 1, 2, 3, 4, 5, 6, and 7 of the trial). Colon tissue samples obtained from the animals were biopsied every other day (on Days 0, 2, 4, 6, 8, and 10 of the trial).

[0056] Data from the biopsies were used to determine an acute inflammation index for each animal, giving a semi-quantitative analysis of the course of the colitis. (See, Madara et al. [18].) The inflammation indices before the trial began (Day 0) and at the end of the trial at Day ...

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Abstract

A method for the treatment of inflammatory bowel disease (IBD) is disclosed. The method comprises administration of an antibody, polypeptide or other molecule recognizing VLA-4, a surface molecule expressed on most types of white blood cells and involved in leukocyte adhesion to endothelium and other tissus in the gut.

Description

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 F...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/16A61K39/00A61K51/00A61P1/00A61K38/00A61K38/17A61P29/00C07K14/705C07K16/28
CPCA61K47/48469A61K47/48476A61K47/48484Y10S514/885A61K51/1027C07K14/70542C07K16/2842A61K47/48561A61K47/6825A61K47/6827A61K47/6829A61K47/6849A61P1/00A61P29/00
Inventor LOBB, ROYBURKLY, LINDA
Owner BIOGEN MA INC
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