Patent application EP16154507A (EP), filed 2016-02-05
Publication number: EP3202788A1
Title: ENDOSIALIN-BINDING ANTIBODY
Abstract: [0001]    The present disclosure relates to the generation of an antibody that specifically recognizes and binds Endosialin, a cell surface antigen characteristic of tumor pericytes and cells of tumor stroma. The antibody has the ability to become internalized in Endosialin expressing cells and to block the activation of MAPK in PDGF stimulated human pericytes. The antibody is able to block angiogenesis induced by LGALS3BP, a known Endosialin interactor and to inhibit tumor growth alone and in combination with 1959, a humanized antibody against LGALS3BP in human osteosarcoma xenograft.
[0002]    The disclosure is also related to nucleotides encoding the antibodies of the invention and cell expressing the antibodies.
IPC codes: A61K  39/   395            A I
A61P  35/    00            A I
C07K  16/    18            A I
C07K  16/    28            A I
G01N  33/   574            A I
Claims: number: 1
text: An antibody or functional fragment thereof, which is directed against an epitope between amino acids 477-488 of human Endosialin according to SEQ ID No: 1.
number: 2
text: The antibody of claim 1 which comprises
number: 3
text: The antibody of claim 1 or 2 which comprises
number: 4
text: The antibody of any one of the previous claims comprising:
number: 5
text: The antibody of any one of the previous claims, which is a Fab fragment, a Fab' fragment, a F(ab') fragment, a Fv- fragment, a diabody, ScFv, SMIP, single chain antibody, affibody, avimer, nanobody and/or a domain antibody.
number: 6
text: The antibody of any one of the previous claims, which is of the IgG1-, IgG2-, IgG3-or IgG4-type or an IgM, IgA1, IgA2, IgAsec, IgD or IgE-type antibody.
number: 7
text: The antibody of any one of the previous claims, which is a monoclonal antibody, in particular a murine antibody, a humanized antibody, a chimeric antibody, a multispecific antibody, in particular a bispecific antibody, or a fragment thereof.
number: 8
text: The antibody of any of the previous claims comprising
a heavy chain variable region comprising an amino acid sequence as shown in SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21 or an amino acid sequence having a identity of at least 90 % thereto, and/or
a light light chain variable region comprising an amino acid sequence as shown in SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24 or SEQ ID NO: 25 or an amino acid sequence having a sequence identity of at least 90 % thereto.
number: 9
text: The antibody of any one of the previous claims, wherein a labeling group and/or to an effector group, preferably a therapeutic group is coupled to the antibody.
number: 10
text: An isolated nucleic acid molecule selected from the group consisting of:
number: 11
text: A vector comprising the nucleic acid sequence of claim 9, preferably an expression vector, wherein the nucleic acid sequence is operably linked to a control sequence.
number: 12
text: A host comprising the nucleic acid of claim 9 or the vector of claim 11, which is preferably a human, bacteria, animal, fungal, amphibian or plant cell, or a non-human transgenic animal.
number: 13
text: A process of manufacturing a monoclonal antibody according to anyone of claims 1-9 comprising the step of obtaining said antibody from the host of claim 12.
number: 14
text: A pharmaceutical composition comprising an antibody of anyone of claims 1-9, a nucleic acid molecule of claim 10, a vector of claim 11, a host of claim 12, or an antibody generated by the process of claim 13, optionally in combination with a pharmaceutically acceptable carrier, diluent, and/or excipient.
number: 15
text: The pharmaceutical composition according to claim 14, comprising a further active agent, such as a further antibody or antibody fragment, in particular an anti-neoplastic agent, preferably selected from the group consisting of antibodies, small molecules, antimetabolites, alkylating agents, topoisomerase inhibitors, microtubule-targeting agents, kinase inhibitors, protein synthesis inhibitors, immuno-therapeutics, hormones or analogs thereof.
number: 16
text: A compound selected from the antibody according to any one of claims 1-9, the nucleic acid molecule of claim 10, the vector of claim 11, the host of claim 12 and the pharmaceutical composition according to claim 15, for use in the prevention or treatment of a neoplastic disease or cancer.
number: 17
text: The compound for the use of claim 16, wherein the disease is neuroblastoma, sarcoma (synovial sarcoma, fibrosarcoma, MFH, liposarcom, osteosarcoma), high-grade glioma, brain tumor, carcinoma (bladder, breast, colon, renal, gastric cancer, endometrial cancer, lung cancer, ovarian cancer) and/or a tumor expressing Endosialin in tumor vasculature and stroma and/or in tumor cells.
number: 18
text: The compound for the use of claim 16 or 17, which is to be administered intravenously, intramuscularly, and/or subcutaneously.
number: 19
text: The compound for the use of any one of claims 16-18, for administration in combination with a further therapeutic composition and/or irradiation.
Office action: search_report, dated 2017-08-09
Rejection reasons: novelty_epc_54
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ref_id: &#91;XDI]     - ZHAO A ET AL: "Rapid isolation of high-affinity human antibodies against the tumor vascular marker Endosialin/TEM1, using a paired yeast-display/secretory scFv library platform", JOURNAL OF IMMUNOLOGICAL METHODS, ELSEVIER SCIENCE PUBLISHERS B.V.,AMSTERDAM, NL, vol. 363, no. 2, 5 January 2011 (2011-01-05), pages 221 - 232, XP027558132, ISSN: 0022-1759, [retrieved on 20101213&#93;
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severity: novelty_destroying
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severity: novelty_destroying
ref_id: - TOMKOWICZ BRIAN ET AL, "Interaction of endosialin/TEM1 with extracellular matrix proteins mediates cell adhesion and migration", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, US, (20071113), vol. 104, no. 46, doi:10.1073/PNAS.0705647104, ISSN 0027-8424, pages 17965 - 17970, XP002494741 [XD] 1,6,7,12-14 * the whole document * [I] 2-5,8-11,15-19
ref_type: npl
severity: novelty_destroying
ref_id: - KATHERINE RYBINSKI ET AL, "Targeting endosialin/CD248 through antibody-mediated internalization results in impaired pericyte maturation and dysfunctional tumor microvasculature", ONCOTARGET, United States, (20150704), vol. 6, no. 28, doi:10.18632/oncotarget.4559, ISSN 1949-2553, pages 25429 - 25440, XP055293248 [X] 1,6,7,14,16-18 * whole document, especially the Abstract and Figures 1-2 * [I] 2-5,8-13,15,19
ref_type: npl
severity: novelty_destroying
ref_id: - SONA KONTSEKOVA ET AL, "Novel monoclonal antibodies specific for CTLD-SSC and sialomucin domains of endosialin, a mural cell marker of tumor vasculature", INTERNATIONAL JOURNAL OF ONCOLOGY, GR, (20120723), vol. 41, doi:10.3892/ijo.2012.1566, ISSN 1019-6439, pages 1365 - 1372, XP055293285 [X] 1,6,7,12-14 * whole document, especially the Abstract, Table 1, Figure 4 * [I] 2-5,8-11,15
ref_type: npl
severity: novelty_destroying
ref_id: - ZHAO A ET AL, "Rapid isolation of high-affinity human antibodies against the tumor vascular marker Endosialin/TEM1, using a paired yeast-display/secretory scFv library platform", JOURNAL OF IMMUNOLOGICAL METHODS, ELSEVIER SCIENCE PUBLISHERS B.V.,AMSTERDAM, NL, vol. 363, no. 2, ISSN 0022-1759, (20110105), pages 221 - 232, (20101213), XP027558132 [XD] 1,5,9,11-14 * whole document, especially the Abstract, Figure 3 * [I] 2-4,6-8,10,15
ref_type: npl
severity: novelty_destroying
Final disposition: pending (2017-08-09)