AU620100B2 – Method of inhibiting the influx of leukocytes into organs during sepsis or other trauma
– Google Patents
AU620100B2 – Method of inhibiting the influx of leukocytes into organs during sepsis or other trauma
– Google Patents
Method of inhibiting the influx of leukocytes into organs during sepsis or other trauma
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Info
Publication number
AU620100B2
AU620100B2
AU36084/89A
AU3608489A
AU620100B2
AU 620100 B2
AU620100 B2
AU 620100B2
AU 36084/89 A
AU36084/89 A
AU 36084/89A
AU 3608489 A
AU3608489 A
AU 3608489A
AU 620100 B2
AU620100 B2
AU 620100B2
Authority
AU
Australia
Prior art keywords
leukocytes
antibody
influx
infectious
administration
Prior art date
1988-06-07
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
AU36084/89A
Other versions
AU3608489A
(en
Inventor
Elaine I. Toumanen
Samuel D. Wright
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Rockefeller University
Original Assignee
Rockefeller University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
1988-06-07
Filing date
1989-06-07
Publication date
1992-02-13
1989-06-07
Application filed by Rockefeller University
filed
Critical
Rockefeller University
1989-12-14
Publication of AU3608489A
publication
Critical
patent/AU3608489A/en
1992-02-13
Application granted
granted
Critical
1992-02-13
Publication of AU620100B2
publication
Critical
patent/AU620100B2/en
2009-06-07
Anticipated expiration
legal-status
Critical
Status
Ceased
legal-status
Critical
Current
Links
Espacenet
Global Dossier
Discuss
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Chemical compound
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Classifications
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
A61K39/00—Medicinal preparations containing antigens or antibodies
A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
C—CHEMISTRY; METALLURGY
C07—ORGANIC CHEMISTRY
C07K—PEPTIDES
C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07K16/2839—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily
C07K16/2845—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily against integrin beta2-subunit-containing molecules, e.g. CD11, CD18
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
A61P11/00—Drugs for disorders of the respiratory system
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
A61P17/00—Drugs for dermatological disorders
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
A—HUMAN NECESSITIES
A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
A61K38/00—Medicinal preparations containing peptides
Description
4| IYL~ i I Form COMMONWEALTH OF AUSTRALIA PATENTS ACT 1952-62 COMPLETE SPECIFICATION
(ORIGINAL)
620 100 FOR OFFICE USE: Application Number: Lodged: Class Int. Class Complete Specification Lodged: Accepted: Published: Prjotiy: RelalIe.Art: o 0 4 e* *e’<9 This document 'ontains the amendments Llowed under Section 83 b, Superviaing Exa:.' r G.l and is fur i.r:nthig o TO BE COMPLETED BY APPLICANT Name of Applicant: THE ROCKEFELLER UNIVERSITY 90 0 @9 Address Actual Inventors 3 for Service: Complete Specification 1230 York Avenue, New York, 10021-6399, United States America Samuel D. WRIGHT v, Elaine I. TUOMANEN R K Maddern Associates, 345 King William Street, Adelaide, South Australia, invention entitled: "METHOD OF INHIBITING INFLUX LEUKOCYTES INTO ORGANS DURING SEPSIS OR OTHER TRAUMA" The following statement a full description this invention, including best method performing it known to Ir us.
1 m~chanism bv which IB4 inhibits sequestration PMN into A4$ *000
C
0000 **00 0* 0C @00 60 09 6000 cee 5 so.
C
*0 @ha* la METHOD TRAUMA described herein was made, in part, course work Research Grants AI22003 HL32418 from National Institutes Health, USPHS.
BACKGROUND INVENTION Leukocytes, especially polymorphonuclear (PMN) leukocytes, circulate blood do not adhere endothelium (the cells lining vessels). Upon introduction an infectious agent, fragments that result death or another inflammatory substance nearby tissues, PMN, are induced bind then migrate tissues. Since can recognize kill many agents, protective mechanism. However, disease 20 circumstances, such as sepsis trauma, react exaggerated deleterious fashion. They may so avidly occlude flow. Once they secrete proteases, reactive oxygen intermediates, other toxic molecules only but also extensive tissue damage. In addition, release mediators alter vascular tone permeability, recruit additional leukocytes site, thus perpetuating inflammation.
Two diseases PMN-mediated damage contributes morbidity mortality endotoxic shock adult respiratory distress syndrome. both instances, lung preferred organ emigration be severe enough cause death.
Adult syndrome (ARDS) non-infectious causes; either r; _mark" I4 'cl i -1 ii: 1 iii j -i iir! Intravenous Formulation IV 2 results similar pathology consequence emigration. associated with infection, use antibiotics magnifies effects inflammation. due mechanism by agents exert their anti-infective effects. For example, administration beta-lactam antibiotic (or cell-wall directed antibiotic), bacteria disintegrate lysis agents. resulting initiate dramatically enhanced response. See Tuomanen et al., Am. Rev. Respir. Dis., 135, 869-874 (1987). Earlier research has indicated inhibition antibiotic-induced inflammation correlates improved 15 setting meningitis; J. Infect. So155, 985-990 (1985) Kadurugamuwa, Program ^o Abstracts 27th ICAA Meeting, p. 205 pneumococcal meningitis, instance, directly correlated amount meningeal inflammation; McAllister 132, 355-360 (1975). Thus, dampening during therapy would advantageous treating infections, particularly ARDS infection.
t fashion, noninfectious origin c likewise useful therapeutic tool physicians.
A molecule on surface mediates adhesion redentiy been defined. That molecule, CD18, thought mediate because (a) monoclonal antibodies against CD18 inhibit binding vitro, injection rabbits prevents normal response 16 infection related auto-immune conditions Type I stimulus, patients genetic defect expression fail endothelial deficient sites infection.
CD18 previously receptor third component complement, C3bi (Wright PNAS, 5699-5703 (1983). A single functions two capacities, cells, C3bi-coated cells.
It object present provide inhibiting influx S.o: organs trauma comprises anti-CD18 antibody active fragment thereof patient need therapy.
o
S
It further treat having caused e anti-CDl8 thereof, therapy.
Another afford afflicted administering antibody, whereby eliminated greatly reduced.
1 4 It still eliminate reduce wherein being administered agent prior to, concurrent with, after, thereby eliminating reducing inflammation.
SUMMARY concerns compositions :leukocytes S"or comprising composition thereof. Highly selected group consisting mAb (hereinafter designated 'as IB4) 60.3 60.3)>Download PDF in English
