Antagonist antibodies against EPHB3

{
  "publication_number": "US8377439B2",
  "country": "US",
  "kind": "B2",
  "title": "Antagonist antibodies against EPHB3",
  "abstract": "EphB3-specific antibodies are provided, along with pharmaceutical compositions containing such antibody, kits containing a pharmaceutical composition, and methods of preventing and treating an EphB3-related disease or disorder.",
  "claims": [
    "1. An isolated antagonist antibody or antigen-binding fragment thereof that comprises the three CDRs of the variable light chain set forth at positions 24 through 34, positions 50 through 56, and positions 89 through 97 of SEQ ID NO 3 and the three CDRs of the variable heavy chain set forth at positions 26 through 35, positions 50 through 64, and positions 99 through 107 of SEQ ID NO: 4, wherein the antibody binds the extracellular domain of EphB3 with an affinity (K D) of 10 −6 M or less.",
    "2. The antibody of claim 1 wherein the antibody is a chimeric antibody, a humanized antibody, a human engineered antibody, a human antibody, a single chain antibody or an antibody fragment.",
    "3. The antibody of claim 1 in which one or two amino acids within either the variable light chain or variable heavy chain have been modified.",
    "4. The antibody of claim 1 that retains 97, 98, or 99% identity over either the variable light chain or variable heavy chain.",
    "5. The antibody of claim 1 comprising a conservative substitution in either the variable light chain or variable heavy chain.",
    "6. The antibody of claim 1 that comprises a constant region of a human antibody sequence and one or more heavy and light chain variable framework regions of a human antibody sequence.",
    "7. The antibody of claim 6 wherein the human antibody sequence is an individual human sequence, a human consensus sequence, an individual human germline sequence, or a human consensus germline sequence.",
    "8. The antibody of claim 1 wherein the heavy chain constant region is a modified or unmodified heavy chain constant region of IgG, IgM, IgA, IgD, IgE, a fragment thereof, or combinations thereof.",
    "9. The antibody of claim 1 wherein the light chain constant region is a modified or unmodified lambda light chain constant region, a kappa light chain constant region, a fragment thereof, or combinations thereof.",
    "10. The antibody of claim 1 that has a binding affinity of 10 −7, 10 −8 or 10 −9 M or less to EphB3.",
    "11. The antibody of claim 1 that inhibits EphB3 phosphorylation.",
    "12. The antibody of claim 1 that inhibits EphB3 dimerization.",
    "13. The antibody of claim 1 that inhibits EphB3 ligand-induced receptor activation.",
    "14. The antibody of claim 1 that inhibits EphB3 signaling.",
    "15. The antibody of claim 1 that inhibits the binding of ephrinB2 to EphB3.",
    "16. The antibody of claim 1 that inhibits the binding of ephrinB1 to EphB3.",
    "17. The antibody of claim 1 that inhibits the binding of ephrinB3 to EphB3.",
    "18. The antibody of claim 1 that inhibits proliferation of an intestinal cell.",
    "19. The antibody of claim 1 that inhibits proliferation of a vascular cell.",
    "20. The antibody of claim 1 that promotes proliferation of a neuronal cell.",
    "21. The antibody of claim 1 that is conjugated to another diagnostic or therapeutic agent.",
    "22. The antibody of claim 1 that is purified to at least 95% homogeneity by weight.",
    "23. A pharmaceutical composition comprising the antibody of claim 22 and a pharmaceutically acceptable carrier.",
    "24. A kit comprising a therapeutically effective amount of an antibody of claim 1, packaged in a container, said kit optionally containing a second therapeutic agent, and further comprising a label attached to or packaged with the container, the label describing the contents of the container and providing indications and/or instructions regarding use of the contents of the container to treat an EphB3-related disease or disorder.",
    "25. The kit of claim 24 wherein the container is a vial or bottle or prefilled syringe."
  ],
  "description_excerpt": "This invention relates to methods for preventing and treating EphB3-related diseases or disorders by administering EphB3-antagonist antibodies.\n\nEphB3 is a receptor in the ephrin receptor tyrosine kinase family. Presently there are 14 Eph receptors and 9 ephrin ligands known in humans. Ephrin receptors (Ephs) and their ligands, the ephrins, mediate numerous developmental processes, particularly in the nervous system and vascular systems. Ephrins are also known to play a role in tumor development, angiogenesis, metastatic growth and cell survival. Based on their structures and sequence relationships, ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. The Eph family of receptors is divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Eph receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family.\n\nEphs appear to function by signaling upon activation. Ephrin binding induces Eph receptor oligomerization causing phosphorylation of juxtamembrane residues of Ephs. Activated Ephs have multiple phosphorylated tyrosines that act as docking sites for signaling proteins (e.g. RasGAP, Src, LMW-PTP, PLCg, PI3-kinase, Grb2, and PDZ containing proteins).\n\nOverexpression of Eph receptors (EphA1, EphA2, EphB2) causes transformation in the absence of receptor hyper-phosphorylation.",
  "cpc": [
    "C07K 16/28",
    "A61K 39/395",
    "A61K 39/3955",
    "A61P 1/00",
    "A61P 15/00",
    "A61P 17/02",
    "A61P 17/06",
    "A61P 19/02",
    "A61P 21/04",
    "A61P 25/00",
    "A61P 25/02",
    "A61P 25/14",
    "A61P 25/16",
    "A61P 25/28",
    "A61P 27/02",
    "A61P 29/00",
    "A61P 31/04",
    "A61P 31/10",
    "A61P 31/12",
    "A61P 35/00",
    "A61P 37/06",
    "A61P 43/00",
    "A61P 9/00",
    "A61P 9/10",
    "C07K 16/18",
    "C07K 16/2866",
    "C07K 2317/622",
    "C07K 2317/76",
    "C07K 2317/92",
    "C12N 2799/026",
    "F01D 25/162",
    "F16B 33/002",
    "F16B 35/048",
    "F16B 43/001",
    "Y02T 50/60"
  ],
  "ipc": [
    "A61K 39/395",
    "C07K 16/00",
    "C07K 16/18",
    "C07K 16/28",
    "C12P 21/08"
  ],
  "assignees": [
    "Novartis AG",
    "Xoma Technology Ltd USA"
  ],
  "inventors": [
    "Ssucheng Jeff Hsu",
    "Linda Masat"
  ],
  "filing_date": "2007-12-06",
  "publication_date": "2013-02-19",
  "grant_date": "2013-02-19",
  "priority_date": "2006-12-07",
  "application_number": "US-31283707-A",
  "family_id": "39204649",
  "cited_by_count": 5,
  "citations": [
    "JPH07165799A",
    "WO1995025167A1",
    "US7517967B2",
    "WO2001019992A2",
    "WO2001071005A2",
    "WO2003087841A2",
    "WO2003086458A1",
    "WO2004005457A2",
    "EP1400807A2",
    "WO2005005638A2",
    "WO2005016381A2",
    "WO2006013904A1",
    "US20060121042A1",
    "WO2006118350A1",
    "WO2006132907A2"
  ]
}