Patents Assigned to Maxygen Holdings, Ltd.
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Patent number: 7550566Abstract: Polypeptide conjugates with G-CSF activity comprising a polypeptide having at least one introduced lysine residue and at least one removed lysine residue compared to the sequence of human G-CSF, and which are conjugated to 2-6 polyethylene glycol moieties. The conjugates have a low in vitro bioactivity, a long in vivo half-life, a reduced receptor-mediated clearance, and provide a more rapid stimulation of production of white blood cells and neutrophils than non-conjugated recombinant human G-CSF.Type: GrantFiled: August 10, 2006Date of Patent: June 23, 2009Assignee: Maxygen Holdings Ltd.Inventors: Torben Lauesgaard Nissen, Kim Vilbour Andersen, Christian Karsten Hansen, Jan Moller Mikkelsen, Hans Thalsgaard Schambye
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Patent number: 7550565Abstract: Polypeptide conjugates with G-CSF activity comprising a polypeptide having at least one introduced lysine residue and at least one removed lysine residue compared to the sequence of human G-CSF, and which are conjugated to 2-6 polyethylene glycol moieties. The conjugates have a low in vitro bioactivity, a long in vivo half-life, a reduced receptor-mediated clearance, and provide a more rapid stimulation of production of white blood cells and neutrophils than non-conjugated recombinant human G-CSF.Type: GrantFiled: August 10, 2006Date of Patent: June 23, 2009Assignee: Maxygen Holdings Ltd.Inventors: Torben Lauesgaard Nissen, Kim Vilbour Andersen, Christian Karsten Hansen, Jan Moller Mikkelsen, Hans Thalsgaard Schambye
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Patent number: 7524931Abstract: The present invention relates to novel full-length interferon gamma (IFNG) polypeptide variants having interferon gamma activity. The full-length interferon gamma polypeptide variants of the invention are obtained by performing selected modifications in the C-terminal part of the molecule. The full-length interferon gamma polypeptide variants of the invention are useful in therapy, in particular for the treatment of interstitial pulmonary diseases, such as idiopathic pulmonary fibrosis.Type: GrantFiled: June 23, 2003Date of Patent: April 28, 2009Assignee: Maxygen Holdings Ltd.Inventors: Bart Van Den Hazel, Anne Dam Jensen, Frank Bechnygaard, Kim Vilbour Andersen
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Patent number: 7504237Abstract: A conjugate exhibiting interferon gamma activity and comprising at least one first non-polypeptide moiety covalently linked to an IFG polypeptide, the polypeptide comprising an amino acid sequence that differs from that of a parent IFNG polypeptide in at least one introduced and/or at least one removed amino acid residue comprising an attachment group for the non-polypeptide moiety. The conjugate may be used for treatment of various diseases.Type: GrantFiled: March 16, 2006Date of Patent: March 17, 2009Assignee: Maxygen Holdings Ltd.Inventors: Anne Dam Jensen, Kim Vilbour Andersen, Christian Karsten Hansen
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Patent number: 7442524Abstract: Conjugates of Factor VII (FVII) and Factor VIIa (FVIIA) are provided, as are methods for preparing them. Methods for producing novel polypeptides contributing to the production of such conjugates are provided. Methods of treatment by administering a FVII or FVIIa conjugate are provided.Type: GrantFiled: June 12, 2006Date of Patent: October 28, 2008Assignee: Maxygen Holdings Ltd.Inventors: Anders Hjelholt Pedersen, Kim Vilbour Andersen, Claus Bornaes
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Patent number: 7427592Abstract: Conjugates of Factor VII (FVII) and Factor VIIa (FVIIA) are provided, as are methods for preparing them. Methods for producing novel polypeptides contributing to the production of such conjugates are provided. Methods of treatment by administering a FVII or FVIIa conjugate are provided.Type: GrantFiled: June 12, 2006Date of Patent: September 23, 2008Assignee: Maxygen Holdings Ltd.Inventors: Anders Hjelholt Pedersen, Kim Vilbour Andersen, Claus Bornaes
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Patent number: 7419805Abstract: The present invention relates to novel interferon gamma polypeptide variants having interferon gamma (IFNG) activity, methods for their preparation, pharmaceutical compositions comprising the polypeptide variants and their use in the treatment of diseases, in particular for the treatment of interstitial pulmonary diseases, such as idiopathic pulmonary fibrosis. These novel polypeptide variants all comprise the substitution S99T as compared to the amino acid sequence of huIFNG or fragments thereof. By performing this mutation the naturally occurring N-glycosylation site present at position 97 is significantly better utilized. Preferably, the variants comprise further modifications, e.g. in order to increase the AUC of such variants when administered subcutaneously.Type: GrantFiled: June 22, 2005Date of Patent: September 2, 2008Assignee: Maxygen Holdings, Ltd.Inventor: Anne Dam Jensen
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Patent number: 7414022Abstract: Conjugates of Factor VII (FVII) and Factor VIIa (FVIIA) are provided, as are methods for preparing them. Methods for producing novel polypeptides contributing to the production of such conjugates are provided. Methods of treatment by administering a FVII or FVIIa conjugate are provided.Type: GrantFiled: June 26, 2006Date of Patent: August 19, 2008Assignee: Maxygen Holdings Ltd.Inventors: Anders Hjelholt Pedersen, Kim Vilbour Andersen, Claus Bornaes
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Patent number: 7390638Abstract: When interferon gamma (IFNG) is produced in mammalian cell lines a heterogenous population of IFNG polypeptides is obtained due to C-terminal processing of the IFNG polypeptide. Clearly, this constitutes a severe problem in that valuable polypeptide material is lost and, further, it is necessary to carry out time-consuming and cumbersome purification in order to obtain a homogenous population of active IFNG polypeptides having the desired length. It has now been found that an IFNG fragment containing 132 amino acid residues (truncated at the nucleotide level by introducing a stop-codon after the codon encoding amino acid residue no. 132) does not undergo C-terminal truncation or, at least, is not significantly C-terminally truncated. Furthermore, as the IFNG fragment containing 132 amino acid residues is active, this opens up the possibility of producing a homogenous active IFNG polypeptide in eukaryotic host cells, such as CHO cells.Type: GrantFiled: April 27, 2005Date of Patent: June 24, 2008Assignee: Maxygen Holdings, Ltd.Inventors: Bart Van Den Hazel, Anne Dam Jensen, Frank Bech Nygaard, Kim Vilbour Andersen
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Patent number: 7381805Abstract: A method for increasing the stability and uniformity of a PEGylated G-CSF polypeptide having at least one PEG moiety attached to the epsilon amino group of a lysine residue or the N-terminal amino group and at least one PEG moiety attached to a hydroxyl group, comprising subjecting the polypeptide to an elevated pH of above 8.0 for a period of time suitable to remove PEG moieties attached to a hydroxyl group, and reducing the pH to about 8.0 or lower; as well as PEGylated G-CSF polypeptides and compositions produced according to the method and methods for increasing neutrophil levels in a patient using the PEGylated G-CSF polypeptides and compositions.Type: GrantFiled: May 26, 2006Date of Patent: June 3, 2008Assignee: Maxygen Holdings, Ltd.Inventors: Carsten Germansen, Bobby Soni, Grethe Rasmussen
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Patent number: 7371543Abstract: Conjugates of Factor VII (FVII) and Factor VIIa (FVIIA) are provided, as are methods for preparing them. Methods for producing novel polypeptides contributing to the production of such conjugates are provided. Methods of treatment by administering a FVII or FVIIa conjugate are provided.Type: GrantFiled: September 27, 2004Date of Patent: May 13, 2008Assignee: Maxygen Holdings Ltd.Inventors: Anders Hjelholt Pedersen, Kim Vilbour Andersen, Claus Bornaes
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Patent number: 7232562Abstract: A conjugate exhibiting interferon gamma activity and comprising at least one first non-polypeptide moiety covalently linked to an IFG polypeptide, the polypeptide comprising an amino acid sequence that differs from that of a parent IFNG polypeptide in at least one introduced and/or at least one removed amino acid residue comprising an attachment group for the non-polypeptide moiety. The conjugate may be used for treatment of various diseases.Type: GrantFiled: February 19, 2003Date of Patent: June 19, 2007Assignee: Maxygen Holdings Ltd.Inventors: Anne Dam Jensen, Kim Vilbour Andersen, Christian Karsten Hansen
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Patent number: 7230081Abstract: A conjugate exhibiting interferon gamma activity and comprising at least one first non-polypeptide moiety covalently linked to an IFG polypeptide, the polypeptide comprising an amino acid sequence that differs from that of a parent IFNG polypeptide in at least one introduced and/or at least one removed amino acid residue comprising an attachment group for the non-polypeptide moiety. The conjugate may be used for treatment of various diseases.Type: GrantFiled: November 13, 2000Date of Patent: June 12, 2007Assignee: Maxygen Holdings, Ltd.Inventors: Anne Dam Jensen, Kim Vilbour Andersen, Christian Karsten Hansen
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Patent number: 7226999Abstract: The present invention relates to novel conjugates between polypeptide variants of protein C and a non-polypeptide moiety, such as PEG or sugar moieties. In particular, the present invention provides novel protein C conjugates having an increased resistance to inactivation by e.g. human plasma and ?1-antitrypsin. Consequently, such conjugates have an increased in vivo half-life. Preferred examples include protein C conjugates, wherein at least one additional in vivo N-glycosylation site has been introduced. The conjugates of the invention are useful for treating a variety of diseases, including septic shock.Type: GrantFiled: December 3, 2004Date of Patent: June 5, 2007Assignees: Maxygen ApS, Maxygen Holdings Ltd.Inventors: Kim Vilbour Andersen, Anders Hjelholt Pedersen, Per Ola Freskgaard
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Publication number: 20070054366Abstract: Variants of FVII or FVIIa comprising at least one amino acid modification in position 196, 237 or 341 relative to hFVII or hFVIIa. The variants exhibit an increased clotting activity, i.e. reduced clotting time, compared to rhFVIIa.Type: ApplicationFiled: March 22, 2004Publication date: March 8, 2007Applicant: MAXYGEN HOLDINGS LTD.Inventors: Kim Andersen, Mads Ropke, Jesper Haaning, Steven Glazer
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Patent number: 7038015Abstract: The present invention relates to novel interferon gamma polypeptide variants having interferon gamma (IFNG) activity, methods for their preparation, pharmaceutical compositions comprising the polypeptide variants and their use in the treatment of diseases, in particular for the treatment of interstitial pulmonary diseases, such as idiopathic pulmonary fibrosis. These novel polypeptide variants all comprise the substitution S99T as compared to the amino acid sequence of huIFNG or fragments thereof. By performing this mutation the naturally occurring N-glycosylation site present at position 97 is significantly better utilized. Preferably, the variants comprise further modifications, e.g. in order to increase the AUC of such variants when administered subcutaneously.Type: GrantFiled: April 4, 2002Date of Patent: May 2, 2006Assignee: Maxygen Holdings, Ltd.Inventor: Anne Dam Jensen
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Patent number: 6933367Abstract: The present invention relates to novel conjugates between polypeptide variants of protein C and a non-polypeptide moiety, such as PEG or sugar moieties. In particular, the present invention provides novel protein C conjugates having an increased resistance to inactivation by e.g. human plasma and ?1-antitrypsin. Consequently, such conjugates have an increased in vivo half-life. Preferred examples include protein C conjugates, wherein at least one additional in vivo N-glycosylation site has been introduced. The conjugates of the invention are useful for treating a variety of diseases, including septic shock.Type: GrantFiled: November 29, 2001Date of Patent: August 23, 2005Assignees: Maxygen Aps, Maxygen Holdings, Ltd.Inventors: Kim Vilbour Andersen, Anders Hjelholt Pedersen, Per Ola Freskgaard
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Patent number: 6831158Abstract: Polypeptide conjugates with G-CSF activity comprising a polypeptide having at least one introduced lysine residue and at least one removed lysine residue compared to the sequence of human G-CSF, and which are conjugated to 2-6 polyethylene glycol moieties. The conjugates have a low in vitro bioactivity, a long in vivo half-life, a reduced receptor-mediated clearance, and provide a more rapid stimulation of production of white blood cells and neutrophils than non-conjugated recombinant human G-CSF.Type: GrantFiled: July 10, 2002Date of Patent: December 14, 2004Assignee: Maxygen Holdings Ltd.Inventors: Torben Lauesgaard Nissen, Kim Vilbour Andersen, Christian Karsten Hansen, Jan Moller Mikkelsen, Hans Thalsgaard Schambye
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Publication number: 20040241806Abstract: The invention relates to polypeptide conjugates comprising a polypeptide exhibiting G-CSF activity and having an amino acid sequence that differs from the amino acid sequence of human G-CSF in at least one specified introduced and/or removed amino acid residue comprising an attachment group for a non-polypeptide moiety, and having at least one non-polypeptide moiety attached to an attachment group of the polypeptide. The attachment group may e.g., be a lysine, cysteine, aspartic acid or glutamic acid residue or a glycosylation site, and the non-polypeptide moiety may e.g., be a polymer such as polyethylene glycol or an oligosaccharide. The conjugate has one or more improved properties such as increased biological half-life and reduced side effects.Type: ApplicationFiled: November 10, 2003Publication date: December 2, 2004Applicant: Maxygen Holdings, Ltd.Inventors: Torben Lauesgaard Nissen, Kim Vilbour Andersen, Christian Karsten Hansen, Jan Moller Mikkelsen, Hans Thalsgard Schambye
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Patent number: 6806063Abstract: Conjugates of Factor VII (FVII) and Factor VIIa (FVIIA) are provided, as are methods for preparing them. Methods for producing novel polypeptides contributing to the production of such conjugates are provided. Methods of treatment by administering a FVII or FVIIa conjugate are provided.Type: GrantFiled: February 12, 2001Date of Patent: October 19, 2004Assignees: Maxygen ApS, Maxygen Holdings Ltd.Inventors: Anders Hjelholt Pedersen, Kim Vilbour Andersen, Claus Bornaes