公开(公告)号：EP1572748B1

公开(公告)日：2010-06-23

申请号：EP03795898.0

申请日：2003-12-16

申请人： Merck Patent GmbH

发明人： GILLIES, Stephen, D. ,  LO, Kin-Ming

IPC分类号： C07K16/30 ,  C12N15/13 ,  C12N5/10 ,  C07K19/00 ,  A61K39/395 ,  C07K16/46

CPC分类号： C07K16/3084 ,  A61K48/00 ,  C07K16/30 ,  C07K16/467 ,  C07K2317/24 ,  C07K2317/732

摘要： The invention provides humanized antibody H14.18 binding the human cell surface glycosphingolipid GD2. The antibody comprises modified variable regions, more specially, modified framework regions, which reduce their immunogenitity when administered to a human. The antibody may be coupled to the therapeutic agent such as IL-2 and used in the treatment of cancer.

公开(公告)号：EP1819728B1

公开(公告)日：2010-04-21

申请号：EP05850240.2

申请日：2005-12-08

申请人： Merck Patent GmbH

发明人： GILLIES, Stephen, D. ,  WAY, Jeffrey, C.

IPC分类号： C07K14/54 ,  C07K16/46 ,  C12N15/24 ,  A61P35/00 ,  A61P31/18

CPC分类号： C07K14/5418 ,  A61K38/00

公开(公告)号：EP1706428B1

公开(公告)日：2009-09-23

申请号：EP05701002.7

申请日：2005-01-18

申请人： Merck Patent GmbH

发明人： GILLIES, Stephen, D.

IPC分类号： C07K16/30 ,  A61P35/00 ,  A61K39/395

CPC分类号： C07K16/3084 ,  A61K2039/505 ,  C07K16/44 ,  C07K2317/52 ,  C07K2317/522 ,  C07K2317/56 ,  C07K2317/732 ,  C07K2317/734

摘要： The invention provides modified antibodies directed against GD2 that have diminished complement fixation relative to antibody-dependent, cell-mediated cytotoxicity, which is maintained. The modified antibodies of the invention may be used in the treatment of tumors such as neuroblastoma, glioblastoma, melanoma, small-cell lung carcinoma, B-cell lymphoma, renal carcinoma, retinoblastoma, and other cancers of neuroectodermal origin.

公开(公告)号：EP1699822A2

公开(公告)日：2006-09-13

申请号：EP04804151.1

申请日：2004-12-21

申请人： Merck Patent GmbH

发明人： LAUDER, Scott ,  GILLIES, Stephen, D.

IPC分类号： C07K14/54 ,  C12N15/62 ,  A61K38/04

CPC分类号： C07K14/5418 ,  A61K38/2046 ,  A61K2039/55527 ,  C07K2319/00 ,  C07K2319/30

摘要： The invention relates to interleukin-7 (IL-7) fusion proteins, methods of their production and uses thereof. The fusion proteins comprise an immunoglobulin portion fused directly or indirectly to IL-7, which was modified at specific positions as compared to the wild­type IL-7 in order to improve biological and pharmaceutical properties. The proteins of the invention are particularly useful in treating disorders accompanied by immune deficiencies and particularly diseases which involve T-cell deficiencies.

公开(公告)号：EP0782625B1

公开(公告)日：2007-05-09

申请号：EP95934426.8

申请日：1995-09-14

申请人： Merck Patent GmbH

发明人： LO, Kin-Ming ,  SUDO, Yukio, c/o Asaka Institute ,  GILLIES, Stephen, D.

IPC分类号： C12N15/62 ,  C12N15/85 ,  C12N5/10 ,  C07K14/705 ,  C07K14/16 ,  C07K16/00

CPC分类号： C07K14/005 ,  C07K14/475 ,  C07K14/55 ,  C07K14/705 ,  C07K14/71 ,  C07K16/00 ,  C07K16/28 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/10 ,  C07K2319/30 ,  C07K2319/32 ,  C07K2319/35 ,  C07K2319/40 ,  C07K2319/50 ,  C07K2319/75 ,  C12N15/62 ,  C12N15/625 ,  C12N15/85 ,  C12N2740/16122 ,  C12N2740/16322

摘要： Disclosed are DNAs produced by recombinant techniques for inducing the expression and subsequent secretion of a target protein. The DNAs encode, in their 5' to 3' direction, a secretion cassette, including a signal sequence and an immunoglobulin Fc region, and a target protein. The DNAs can be transfected into a host cell for the expression, production and subsequent secretion of the target protein as a fusion protein. The secreted protein can be collected from the extracellular space, and further purified as desired. The secreted fusion protein additionally can be proteolytically cleaved to release the target protein from the secretion cassette.

公开(公告)号：EP1761559A2

公开(公告)日：2007-03-14

申请号：EP05766761.0

申请日：2005-06-28

申请人： Merck Patent GmbH

发明人： GILLIES, Stephen, D. ,  WATKINS, Nigel, John ,  BAKER, Matthew, Paul ,  LO, Kin-Ming

IPC分类号： C07K14/565

CPC分类号： C07K16/46 ,  A61K38/00 ,  A61K47/48423 ,  A61K47/6813 ,  C07K14/565 ,  C07K2319/30

摘要： Disclosed are Fc-interferon-beta (Fc-IFN-β) fusion proteins and nucleic acid molecules encoding them. The Fc- IFN-β fusion proteins include variants of the interferon-beta (IFN-β) protein that are altered to achieve enhanced biological activity, prolonged circulating half-life and greater solubility. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins and/or nucleic acid molecules for treating diseases and conditions alleviated by the administration of interferon-beta.

公开(公告)号：EP1699821B1

公开(公告)日：2012-06-20

申请号：EP04804204.8

申请日：2004-12-22

申请人： Merck Patent GmbH

发明人： GILLIES, Stephen, D. ,  LAUDER, Scott ,  MUELLER, Robert ,  KRESS, Dorothee ,  MAHLER, Hanns-Christian

IPC分类号： C07K14/505

CPC分类号： C07K14/505 ,  A61K39/395 ,  C07K2319/30

摘要： The present invention provides novel highly sialylated Fc-EPO fusion proteins preferably comprising a couple of modifications in the Fc- portion as well as in the EPO portion and having improved pharmacokinetics. Specifically, the Fc-EPO proteins have a prolonged serum half-life and increased in vivo potency. The Fc-EPO fusion proteins synthesized in BHK cells have dramatically prolonged serum half-lives and increased in vivo potency when compared to corresponding Fc-EPO fusion proteins produced in other cell lines, such as, for example, NS/O cells.

公开(公告)号：EP1373301B1

公开(公告)日：2010-12-01

申请号：EP02757870.7

申请日：2002-03-30

申请人： Merck Patent GmbH

发明人： GILLIES, Stephen, D.

IPC分类号： C07K1/00

CPC分类号： C07K1/1077 ,  C07K14/505 ,  C07K14/5434 ,  C07K14/55 ,  C07K14/70578 ,  C07K16/30 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/30 ,  C07K2319/33 ,  C07K2319/40 ,  C07K2319/75 ,  C12N15/62 ,  Y10S424/809 ,  Y10S530/868

摘要： Disclosed are compositions and methods for producing fusion proteins with reduced immunogenicity. Fusion proteins of the invention include a junction region having an amino acid change that reduces the ability of a junctional epitope to bind to MHC Class II, thereby reducing its interaction with a T-cell receptor. Methods of the invention involve analyzing, changing, or modifying one or more amino acids in the junction region of a fusion protein in order to identify a T-cell epitope and reduce its ability to interact with a T-cell receptor. Compositions and methods of the invention are useful in therapy.

公开(公告)号：EP1107989B1

公开(公告)日：2010-03-31

申请号：EP99942468.2

申请日：1999-08-25

申请人： Merck Patent GmbH

发明人： LO, Kin-Ming ,  LI, Yue ,  GILLIES, Stephen, D.

IPC分类号： C07K14/78 ,  C07K14/515 ,  C12N9/68 ,  C12N15/62 ,  C07K19/00

CPC分类号： A61K38/00 ,  C07K14/515 ,  C07K14/78 ,  C07K2317/24 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/30 ,  C07K2319/75 ,  C12N9/6435 ,  C12N15/62 ,  C12Y304/21007 ,  Y10S530/81

摘要： Disclosed are nucleotide sequences, for example, DNA or RNA sequences, which encode an immunoglobulin Fc-angiogenesis inhibitor fusion protein. The angiogenesis inhibitors can be angiostatin, endostatin, a plasminogen fragment having angiostatin activity, or a collagen XVIII fragment having endostatin activity. The nucleotide sequences can be inserted into a suitable expression vector and expressed in mammalian cells. Also disclosed is a family of immunoglobulin Fc-angiogenesis inhibitor fusion proteins that can be produced by expression of such nucleotide sequences. Also disclosed are methods using such nucleotide sequences and fusion proteins for treating conditions mediated by angiogenesis.

公开(公告)号：EP1454138A2

公开(公告)日：2004-09-08

申请号：EP02792325.9

申请日：2002-12-04

申请人： MERCK PATENT GmbH

发明人： GILLIES, Stephen, D.

IPC分类号： G01N33/53 ,  G01N33/567

CPC分类号： C07K14/55 ,  C07K2319/00

摘要： The invention provides cytokine fusion proteins, with an increased therapeutic index and methods to increase the therapeutic index of such fusion proteins. The fusion proteins of the invention are able to bind to more than one type of cytokine receptor expressed on cells and also bind to more than one cell type. In addition, the fusion proteins of the invention exhibit a longer circulating half-life in a patient's body than the corresponding naturally occurring cytokine.