Biotempt B.v.

Erasmus Universiteit Rotterdam

Biotemp B.v.

Robbert Benner

Nisar Ahmed Khan

Richard Michael Carlton

Gert Wensvoort

Hubertus Franciscus Josef Savelkoul

Leonie A Boven

Bartholomeus Caspar J Jacobs

Johannes N M Yzermans

The invention relates to acetates of the tetrapeptides AQGV (SEQ ID NO:2) and LQGV (SEQ ID NO:3), pharmaceutical compositions comprising the acetates of the tetrapeptides, and methods of treating using the acetates of the tetrapeptides or pharmaceutical compositions to treat acute inflammatory conditions including sepsis.

Oligopeptide acetate and formulations thereof

Methods of treating radiation injury of a subject in need thereof comprising administering to the subject a peptide consisting of an amino acid molecule selected from the group consisting of VVC, LAG, AQG, LQGV, QVVC, MTRV, LAGV, LQAV, PGCP, VGQL, RVLQ, EMFQ, AVAL, FVLS, NMWD, LCFL, FSYA, FWVD, AFTV, LGTL, QLLG, YAIT, APSL, ITTL, QALG, GVLC, NLIN, SPIE, LNTI, LHNL, CPVQ, EVVR, MTEV, EALE, EPPE, LGTL, VGGI, RLPG, LQGA, LCFL, TLAVE, VEGNL, LNEAL, CPRGVNP, MGGTWA, LTCDDP, VCNYRDV, QPLAPLVG, and DINGFLPAL. The invention provides for administration of the peptide prior to and following exposure of the subject to a source of radiation.

Control of radiation injury

The invention relates to the treatment of an ischemic event such as a stroke or myocardial infarction. The invention provides a method for modulating an ischemic event in a subject comprising providing the subject with a gene-regulatory peptide or functional analogue thereof. Furthermore, the invention provides use of an NF-&#x3ba;B-down-regulating peptide or functional analogue thereof for the production of a pharmaceutical composition for the treatment of reperfusion injury occurring after an ischemic event in a subject.

Treatment of ischemic events

The invention relates to compounds exhibiting immuno-regulatory activity as determined by measuring the compound's ability to modulate production of NO by a cell. Preferred compounds include or consist of a sequenceAAL AAQ AAG AAVwherein AAL is a substituted or unsubstituted non-polar amino acid selected from the group consisting of Ala and Leu; wherein AAQ is a substituted or unsubstituted amino acid selected from the group consisting of Gln, Pro, and Ala; wherein AAG is a substituted or unsubstituted amino acid Gly, and wherein AAV is a substituted or unsubstituted non-polar amino acid selected from the group consisting of Val and Ala. In one embodiment, the compound consists of a tripeptide selected from the group AQG, MTR, VVC, and mixtures thereof.

Immunoregulatory compositions

The invention includes a method of reducing urea concentration in a subject's serum. Such a method comprises administering to the subject (e.g., a mammal such as a human) a composition comprising an oligopeptide (or oligopeptides) having activity in reducing urea concentration in the subject's serum as determined by a mouse renal reperfusion test, wherein the oligopeptide comprises the sequence AQG or MTRV (SEQ ID NO:1), AQGV (SEQ ID NO:2) or LAGV (SEQ ID NO:4).

Compositions capable of reducing elevated blood urea concentration

The invention relates to the field of immunology, more specifically to the field of immune-mediated disorders such as allergies, auto-immune disease, transplantation-related disease or inflammatory disease. The invention provides among others an immunoregulator (NMPF), use of an NMPF in preparing a pharmaceutical composition for treating an immune-mediated disorder, a pharmaceutical composition and a method for treating an immune-mediated disorder.

Immunoregulator

The invention relates to the field of immunology. Specifically, the invention relates to the field of immune-mediated disorders such as allergies, auto-immune disease, transplantation-related disease or inflammatory disease. The invention provides for an immunoregulator (IR), use of an IR in preparing a pharmaceutical composition for treating an immune-mediated disorder and a method for treating an immune-mediated disorder.

Methods of selecting immunoregulator peptides obtained from gonadotropins

Methods of treating radiation injury of a subject in need thereof comprising administering to the subject a peptide consisting of the amino acid sequence AQGV. The invention provides for administration of the amino acid composition prior to and following exposure of the subject to a source of radiation.

The invention relates to the treatment of burn injuries. Described are methods for modulating a burn injury in a subject, the method comprising providing the subject with a gene-regulatory peptide or functional analogue thereof, e.g., LQG, AQG, LQGV (SEQ ID NO:1), AQGV (SEQ ID NO:2), LQGA (SEQ ID NO:3), VLPALP (SEQ ID NO:4), ALPALP (SEQ ID NO:5), VAPALP (SEQ ID NO:6), ALPALPQ (SEQ ID NO:7), VLPAAPQ (SEQ ID NO:8), VLPALAQ (SEQ ID NO:9), LAGV (SEQ ID NO:10), VLAALP (SEQ ID NO:11), VLPALA (SEQ ID NO:12), VLPALPQ (SEQ ID NO:13), VLAALPQ (SEQ ID NO:14), VLPALPA (SEQ ID NO:15), GVLPALP (SEQ ID NO:16), LPGC (SEQ ID NO:19), MTRV (SEQ ID NO:20), MTR, and VVC. Also described is the use of an NF-kappaB down-regulating peptide or functional analogue thereof for the production of a pharmaceutical composition for the treatment of burn injury of a subject.

Treatment of burns

Where it was generally thought that the smallest breakdown products of proteins had no specific biological function on their own, it now emerges that the body may utilize the normal process of proteolytic breakdown to generate important compounds such as gene-regulatory or anti-tumor compounds. Such anti-tumor compounds are useful for the treatment or prevention of tumors and can be used as part of a pharmaceutical composition. The invention provides a pharmaceutical composition for the treatment of a subject suffering from or believed to be suffering from a tumor, said pharmaceutical composition comprising: a therapeutically effective amount of anti-tumor peptide or a functional analogue or derivative thereof together with a pharmaceutically acceptable diluent, wherein the peptide is preferably selected from the group VVC, LAG, AQG, LQGV (SEQ ID NO:1), QVVC (SEQ ID NO:), MTRV (SEQ ID NO:6), AQGV (SEQ ID NO:2), LAGV (SEQ ID NO:3), LQAV (SEQ ID NO:7), PGCP (SEQ ID NO:8), VGQL (SEQ ID NO:9), RVLQ (SEQ ID NO:10), EMFQ (SEQ ID NO:11), AVAL (SEQ ID NO:12), FVLS (SEQ ID NO:13), NMWD (SEQ ID NO:14), LCFL (SEQ ID NO:15), FSYA (SEQ ID NO:16), FWVD (SEQ ID NO:17), AFTV (SEQ ID NO:18), LGTL (SEQ ID NO:19), QLLG (SEQ ID NO:20), YAIT (SEQ ID NO:21), APSL (SEQ ID NO:22), ITTL (SEQ ID NO:23), QALG (SEQ ID NO:24), GVLC (SEQ ID NO:25), NLIN (SEQ ID NO:26), SPIE (SEQ ID NO:27), LNTI (SEQ ID NO:28), LHNL (SEQ ID NO:29), CPVQ (SEQ ID NO:30), EVVR (SEQ ID NO:31), MTEV (SEQ ID NO:32), EALE (SEQ ID NO:33), TLAVE (SEQ ID NO:38), VEGNL (SEQ ID NO:39), LNEAL (SEQ ID NO:40), VLPALP (SEQ ID NO:4), MGGTWA (SEQ ID NO:41), LTCDDP (SEQ ID NO:42), VLPALPQ (SEQ ID NO:43), VCNYRDV (SEQ ID NO:44), CPRGVNP (SEQ ID NO:45), QPLAPLVG (SEQ ID NO:46) or DINGFLPAL (SEQ ID NO:47).

Treatment of tumors using short peptides from human chorionic gonadotropin (HCG)

The invention relates to the treatment multiple sclerosis, and in particular to the treatment of the inflammatory injury seen in the progressive stages in the disease such as seen with the recurrent upsurges of acute disease, classically known as 'relapses' or 'exacerbations' or &#x201c;relapsing/remitting&#x201d; disease seen in multiple sclerosis. The invention provides a method for modulating a relapsing/remitting disease in a subject suffering therefrom involving providing the subject with a gene-regulatory peptide or functional analogue thereof. Furthermore, the invention provides the use of an NF-&#x3ba;B down-regulating peptide or functional analogue thereof for the production of a pharmaceutical composition for the treatment of relapsing/remitting disease as seen with multiple sclerosis.

Treatment of multiple sclerosis (MS)

The invention provides a method for assessing or determining activity of a test compound on modulation of gene product levels comprising culturing cells, contacting at least one of the cultured cells with a lipid-rich fraction, contacting at least one of the cultured cells with said test compound, determining the presence of a gene product of at least one cell of the cultured cells, and optionally determining the presence of the gene product of at least one cultured cell not contacted with said test compound. To assess human conditions most fully, it is preferred that the cell is of human origin, for example a peripheral blood monocyte taken from a healthy donor.

Compounds of therapeutic value in the treatment of multiple sclerosis and other diseases wherein foamy cells are involved in the disease etiology

The invention relates to the field of immunology, more specifically to the field of immune-mediated disorders such as allergies, auto-immune disease, transplantation-related disease and other inflammatory diseases. The invention in particular relates to the systemic treatment of inflammatory disease by oral or mucosal administration of a pharmaceutical composition with a gene-regulatory peptide. The invention provides a pharmaceutical composition in a form for mucosal application for the treatment of a subject suffering from disease, the pharmaceutical composition comprising a pharmacologically effective amount of a gene-regulatory peptide or a functional analogue thereof together with a pharmaceutically acceptable diluent.

Treatment of type I diabetes

The invention relates to the field of transplantation medicine and to the prevention and treatment of rejection, in particular of chronic rejection, of a transplant by a recipient of the transplant. The invention provides method for modulating transplant survival in a recipient of the transplant comprising providing the transplant with a gene-regulatory peptide or functional analogue thereof. Furthermore, the invention provides use of a gene-regulatory peptide or functional analogue thereof for the production of a pharmaceutical composition for the treatment of a transplant allowing modulating transplant survival in a recipient of the transplant.

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Barendrecht, Netherlands

Robbert Benner