Abstract: There are provided monoclonal antibodies to the LDL receptor which are useful for the identification and purification of LDL and in treatment of e.g. hepatitis C infection.
Type:
Grant
Filed:
March 8, 2001
Date of Patent:
February 1, 2005
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Nachum Yonah, Dany Suissa, Ilana Belzer, Francesco Antonetti, Moshe Smolarsky, Michel Dreano
Abstract: The present invention relates to IL-6 antagonist peptides, isolatable from a peptide library through the two-hybrids system by their ability to bind to the intracellular domain of gp130 and containing at least 5 amino acids. In particular, such peptides comprise the amino acid sequence SEQ ID NO: 6, as well as salts, functional derivatives, precursors and analogs thereof. The present invention also provides the peptides in substantially purified form, in order to be suitable for use in pharmaceutical compositions as active ingredient in pathologies that require IL-6 activity inhibition.
Type:
Grant
Filed:
February 4, 2003
Date of Patent:
January 4, 2005
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Ottaviano Serlupi-Crescenzi, Alessandro Bressan, Linda Della Pietra, Anna Rita Pezzotti
Abstract: Interferon-beta liquid formulations stabilized with a polyol, a non-reducing sugar or a amino acid. In particular, the formulations are stabilized with a polyol, such as mannitol. The formulations, preferably, furthermore comprise a buffer, such as acetate buffer, at a pH comprised between 3.0 and 4.0 and human albumin at a minimum quantity. The interferon-beta is preferably recombinant.
Type:
Application
Filed:
July 16, 2004
Publication date:
December 30, 2004
Applicant:
Applied Research Systems ARS Holding N.V.
Abstract: A hybrid protein includes two coexpressed amino acid sequences forming a dimer. Each sequence contains the binding portion of a receptor, such as TBP1 or TBP2, or a ligand, such as IL-6, IFN-&bgr; and TPO, linked to &agr; subunit of a natural heterodimeric scaffold. Each coexpressed sequence contains a corresponding subunit so as to form a heterodimer upon expression. Corresponding DNA molecules, expression vectors and host cells are also disclosed as are pharmaceutical compositions and a method of producing such proteins.
Type:
Application
Filed:
December 1, 2003
Publication date:
November 18, 2004
Applicant:
Applied Research Systems ARS Holding N.V.
Inventors:
Robert K. Campbell, Bradford A. Jameson, Scott C. Chappel
Abstract: The present invention is related to substituted amine derivatives notably for use as pharmaceutically active compounds, as well as to pharmaceutical formulations containing such amine derivatives of formula (I). Said substituted amine derivatives are efficient modulators, in particular inhibitors, of the Bax function and/or activation. The present invention is furthermore related to novel substituted amine derivatives as well as methods of their preparation.
Type:
Grant
Filed:
December 26, 2002
Date of Patent:
August 3, 2004
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Serge Halazy, Matthias Schwarz, Bruno Antonsson, Agnes Bombrun, Jean-Claude Martinou, Dennis Church
Abstract: The present invention refers to a process for the preparation of (1H)-benzo[c]quinolizin-3-ones derivatives of general formula (I) which involves only three steps and the use, as starting products, of commercially available, or easily preparable, compounds. The compounds of formula (I) are useful as inhibitors of 5&agr;-reductases.
Type:
Grant
Filed:
May 25, 2001
Date of Patent:
April 20, 2004
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Antonio Guarna, Mario Serio, Ernesto Occhiato
Abstract: The present invention provides novel isolated ARP/BRP polynucleotides and the membrane-associated or secreted polypeptides encoded by the ARP/BRP polynucleotides. Also provided are ARP and BRP protein multimers. Further provided are the antibodies that immunospecifically bind to a ARP/BRP polypeptide or any derivative, variant, mutant or fragment of the ARP/BRP polypeptide, a ARP/BRP multimer polynucleotide or antibody. The invention additionally provides methods in which the ARP/BRP polypeptide, multimer, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states, e.g. reproductive disorder, as well as to other uses.
Type:
Application
Filed:
June 5, 2003
Publication date:
April 15, 2004
Applicant:
Applied Research Systems ARS Holding N.V.
Inventors:
Nabil El Taylor, Susan Kiernan, Robert K. Campbell, Christie A. Kelton, Chaomei He
Abstract: Tumor necrosis factor antagonists are administered in therapeutically effective doses to treat and/or prevent endometriosis. The antagonists of this invention typically are selected among various classes of molecules but preferably are soluble TNF receptors. The antagonists are useful for the regression of endometriotic lesions and, if combined with other active ingredients, for amelioration of related disorders, like infertility.
Type:
Application
Filed:
September 22, 2003
Publication date:
March 25, 2004
Applicant:
Applied Research Systems ARS Holding N.V.
Inventors:
Francesco Borrelli, Mauro D'Antonio, Fabrizio Martelli
Abstract: The invention refers to liquid pharmaceutical compositions containing hCG stabilised with a polyalcohol or a non-reducing sugar. Preferably, the compositions are stabilised with mannitol.
In the preferred embodiments such compositions are aqueous solutions in a phosphate buffer at pH 7.
Such compositions are ready to be injected and, therefore, the step of reconstitution of the lyophilised powder is avoided, thus simplifying the way of use.
Type:
Grant
Filed:
November 21, 1997
Date of Patent:
March 16, 2004
Assignee:
Applied Research System ARS Holding N.V.
Abstract: Pathological regional adipose tissue accumulation associated with HIV-associated dysmorphic/dysmetabolic syndrome (HADDS) which may occur with or without subcutaneous adipose tissue lipodystrophy (and which is also described as HIV-associated adipose redistribution syndrome or HARS and other specific medical terms), is treated by administering an effective amount of human growth hormone or other substance which binds to and initiates signalling of the hGH receptor. Alternatively, a substance which stimulates production of endogenous hGH, such as human growth hormone releasing hormone, may be administered. HADDS and related syndromes include abnormal adipose tissue accumulation in the visceral, submandibular, supraclavicular, pectoral, mammary and/or dorsocervical (buffalo hump) area, and/or with subcutaneous lipomas, with or without associated metabolic or other physiologic abnormalities.
Type:
Grant
Filed:
December 30, 1999
Date of Patent:
February 24, 2004
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: A method is described for the site-specific preparation of hGRF-PEG conjugates containing one or more PEG units (per mole of hGRF) covalently bound to Lys 12 and/or Lys 21 and/or N &agr; , characterized in that the conjugation reaction between the hGRF peptide and activated PEG is carried out in solution and the desired hGRF-PEG conjugate can be purified by chromatography. The conjugates prepared by this method, as well as their use in the treatment, prevention or diagnosis of growth hormone deficiency, are also an object of the present invention.
Type:
Application
Filed:
November 20, 2002
Publication date:
February 12, 2004
Applicant:
Applied Research Systems ARS Holding N.V.
Inventors:
Francesco Maria Veronese, Paolo Caliceti, Oddone Schiavon
Abstract: Tumor necrosis factor antagonists are administered in therapeutically effective doses to treat and/or prevent endometriosis. The antagonists of this invention typically are selected from among several classes but preferably are soluble TNF receptors. The antagonists are useful for the regression of endometriotic lesions and, if combined with other active ingredients, for amelioration of related disorders, like infertility.
Type:
Grant
Filed:
September 14, 2001
Date of Patent:
December 16, 2003
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Francesco Borrelli, Mauro D'Antonio, Fabrizio Martelli
Abstract: A hybrid protein includes two coexpressed amino acid sequences forming a dimer. Each sequence contains the binding portion of a receptor, such as TBP1 or TBP2, or a ligand, such as IL-6, IFN-&bgr; and TPO, linked to a subunit of a heterodimeric proteinaceous hormone, such as hCG. Each coexpressed sequence contains a corresponding hormone subunit so as to form a heterodimer upon expression. Corresponding DNA molecules, expression vectors and host cells are also disclosed as are pharmaceutical compositions and a method of producing such proteins.
Type:
Grant
Filed:
January 9, 2001
Date of Patent:
December 16, 2003
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Robert K. Campbell, Bradford A. Jameson, Scott C. Chappel
Abstract: The present invention provides novel isolated ARP/BRP polynucleotides and the membrane-associated or secreted polypeptides encoded by the ARP/BRP polynucleotides. Also provided are ARP and BRP protein multimers. Further provided are the antibodies that immunospecifically bind to a ARP/BRP polypeptide or any derivative, variant, mutant or fragment of the ARP/BRP polypeptide, a ARP/BRP multimer polynucleotide or antibody. The invention additionally provides methods in which the ARP/BRP polypeptide, multimer, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states, e.g. reproductive disorder, as well as to other uses.
Type:
Application
Filed:
February 6, 2003
Publication date:
November 27, 2003
Applicant:
Applied Research Systems ARS Holding N.V.
Inventors:
Nabil El Tayar, Susan Kiernan, Robert K. Campbell, Christie A. Kelton, Chaomei He
Abstract: “The present invention provides non-peptidic amino derivatives, their therapeutic use as well as pharmaceutical compositions that possess activity as Follicle Stimulating Hormone (FSH) agonists and are useful in the treatment of infertility. In particular, the invention provides derivatives.
Type:
Grant
Filed:
May 28, 2002
Date of Patent:
November 25, 2003
Assignee:
Applied Research Systems ARS Holding N.A.
Inventors:
Nabil El Tayer, Adulla Reddy, David Buckler, Sharad Magar
Abstract: A device for reconstituting liquid for medical use by bringing together a first liquid medium contained in a first vessel in the form of a cartridge (3) and a second medium, such as a drug in solid form, contained in a second vessel in the form of a vial (7), the device (19) comprising means (41) for supporting the first and second vessels, and a movable operating member (50) for applying a force to cause the first liquid medium to be delivered at a controlled rate from the first vessel into the second vessel. The first and second vessels may be provided in a pack (70) having liquid transfer means in the form of a needle (10).
Type:
Grant
Filed:
March 16, 1999
Date of Patent:
November 11, 2003
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Grenville Arthur Robinson, Michael Anthony Hobbs, Martyn Omar Rowlands, John Richard Calvert
Abstract: PEG-IFN-&bgr; conjugates, where a PEG moiety is covalently bound to Cys17 of human IFN-&bgr;, are produced by a process of site specific PEGylation with a thiol reactive PEGylating agent. A pharmaceutical composition and a method for treating infections, tumors and autoimmune and inflammatory diseases are also provided. The invention further relates to a method for the stepwise attachment of PEG moieties in series to a polypeptide, and more particularly to IFN-&bgr;.
Type:
Grant
Filed:
October 30, 2000
Date of Patent:
October 28, 2003
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Nabil El-Tayar, Michael J. Roberts, Milton Harris, Wayne Sawlivich
Abstract: The bioactivity of TNF is inhibited by administering heparin or a derivative thereof along with a soluble TNF receptor. The heparin or derivative thereof can be administered simultaneously with the soluble TNF receptor, either in separate compositions or in compositions containing both heparin or a derivative thereof and at least one soluble TNF receptor. The heparin or derivative may also be administered without the soluble TNF receptor and still effect some amount of inhibition of TNF bioactivity.
Type:
Grant
Filed:
November 20, 2000
Date of Patent:
August 19, 2003
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: The present invention relates to IL-6 antagonist peptides, isolatable from a peptide library through the two-hybrids system by their ability to bind to the intracellular domain of gp 130 and containing at least 5 amino acids. In particular, such peptides comprise an amino acid sequence, which is selected from the group consisting of: SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 SEQ ID NO: 8 as well as salts, functional derivatives, precursors and analogs thereof. Another object of the present invention is to provide the peptide in substantially purified form, in order to be suitable for use in pharmaceutical compositions as active ingredient in pathologies that require IL-6 activity inhibition.
Type:
Grant
Filed:
November 20, 2000
Date of Patent:
July 29, 2003
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Ottaviano Serlupi-Crescenzi, Alessandro Bressan, Linda Della Pietra, Anna Rita Pezzotti
Abstract: Soluble polypeptide fraction consisting of all or part one of at least one of the four immunoglobulin-type extracellular LAG-3 protein domains (amino acids 1-159, 160-230 239, 240-330 and 331-412 of the SEQ ID NO:1 sequence) or consisting of one peptide sequence derived from these domains by replacement, addition or deletion of one or more amino acids. The fraction of the invention has a specificity at least equal to that of LAG-3 in relation to its ligand.
Type:
Grant
Filed:
August 17, 2001
Date of Patent:
November 11, 2003
Assignees:
Institut Gustave Roussy, Institut National de la Sante et de la Recherche Medicale
(INSERM), Applied Research System ARS Holding N.V.