Patent application EP19183405A (EP), filed 2019-06-28
Publication number: EP3757125A1
Title: ANTIBODY DIRECTED AGAINST THE APOE AMINO-TERMINAL FRAGMENT OF 12 KDA
Abstract: [0001]    The disclosure relates to an antibody or antigen binding portion thereof, which binds to a neo-epitope of a C-terminal fragment of apolipoprotein E, to methods of producing such an antibody or antigen binding portion thereof, and to therapeutic and diagnostic uses thereof.
IPC codes: A61P  25/    28            A I
C07K  16/    18            A I
Claims: number: 1
text: An antibody or antigen binding portion thereof that binds to a fragment of apolipoprotein E (ApoE), wherein the fragment has
number: 2
text: The antibody or antigen binding portion thereof according to claim 1, wherein the antibody or antigen binding portion thereof binds selectively to the ApoE fragment and does not bind to full-length apolipoprotein E.
number: 3
text: The antibody or antigen binding portion thereof according to claim 1 or claim 2, wherein said fragment of apolipoprotein E is selected from
number: 4
text: The antibody or antigen binding portion thereof according to any one of claims 1-3, wherein the antibody or antigen binding portion thereof binds to an epitope comprising amino acid residues selected from the following:
number: 5
text: The antibody or antigen binding portion thereof according to any one of claims 1-4, wherein said fragment of apolipoprotein E consists of the amino acid sequence SEQ ID NO:1, optionally wherein the epitope comprises amino acid residues 200-205 in full-length apolipoprotein E.
number: 6
text: A method of producing an antibody or an antigen binding portion thereof, comprising a step of immunizing a host mammal with a peptide immunogen comprising an N-terminal amino acid sequence selected from the group consisting of LAGQPL (SED ID NO:4), AGQPLQ (SEQ ID NO:5), GQPLQE (SEQ ID NO:6), LAGQPLQ (SEQ ID NO:7), AGQPLQE (SEQ ID NO:8) and LAGQPLQE (SEQ ID NO:9).
number: 7
text: The method according to claim 6, wherein said N-terminal amino acid sequence is GQPLQE (SEQ ID NO:6).
number: 8
text: An antibody or antigen binding portion thereof, obtainable by a method according to claim 6 or claim 7.
number: 9
text: The antibody or antigen binding portion thereof according to any one of claims 1-5 or 8, wherein the antibody or antigen binding portion thereof comprises a variable heavy chain domain (VH) comprising three CDR sequences (CDR-H1, CDR-H2 and CDR-H3), wherein the three VH CDR sequences are independently selected from:
number: 10
text: The antibody or antigen binding portion thereof according to any one of claims 1-5 and 8-9, wherein the antibody or antigen binding portion thereof comprises a variable light chain domain (VL) comprising three CDR sequences (CDR-L1, CDR-L2 and CDR-L3), wherein the three VL CDR sequences are independently selected from:
number: 11
text: The antibody or antigen binding portion thereof according to any one of claims 1-5 and 8-10, wherein the antibody or antigen binding portion thereof comprises a heavy chain variable domain (VH) comprising or consisting of an amino acid sequence selected from:
number: 12
text: The antibody or antigen binding portion thereof according to any one of claims 1-5 and 8-11, wherein the antibody or antigen binding portion thereof comprises a light chain variable domain (VL) comprising or consisting of an amino acid sequence selected from:
number: 13
text: A pharmaceutical composition comprising an antibody or antigen binding portion thereof according to any one of claims 1-5 and 8-12 and at least one pharmaceutically acceptable excipient or carrier.
number: 14
text: An antibody or antigen binding portion thereof according to any one of claims 1-5 and 8-12, or pharmaceutical composition according to claim 13, for use in therapy.
number: 15
text: A method of detecting or diagnosing a neurological disorder or a disorder characterized by a loss of cognitive memory capacity in a subject, the method comprising contacting a sample obtained from the subject with an antibody or antigen binding portion thereof according to any one of claims 1-5 and 8-12.
Office action: search_report, dated 2020-12-30
Rejection reasons: novelty_epc_54
inventive_step_epc_56
Prior art cited: ref_id: - SOLOMON, EXPERT OPIN. INVESTIG. DRUGS, vol. 16, no. 6, 2007, pages 819 - 828
ref_type: npl
severity: background
ref_id: - MUNOZ ET AL., NEUROCHEM RES, vol. 44, no. 6, 2019, pages 1297 - 1305
ref_type: npl
severity: background
ref_id: - WELLNITZ ET AL., J NEUROCHEM, vol. 94, 2005, pages 1351 - 1360
ref_type: npl
severity: background
ref_id: - MAHLEYHUANG, NEURON, vol. 76, 2012, pages 871 - 885
ref_type: npl
severity: background
ref_id: - MOUCHARD ET AL., SCI REP, vol. 9, no. 1, 2019, pages 3989
ref_type: npl
severity: background
ref_id: - DARLINGBRAULT: "Assay and Drug Dev Tech", vol. 2, 2004, SAPIDYNE INSTRUMENTS INC, pages: 647 - 657
ref_type: npl
severity: background
ref_id: - WANG ET AL., JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 96, 2007, pages 1 - 26
ref_type: npl
severity: background
ref_id: US2017218058A1
ref_type: patent
severity: background
ref_id: - BENTLEY N M ET AL: "Apolipoprotein E structural requirements for the formation of SDS-stable complexes with beta-amyloid-(1-40): the role of salt bridges", BIOCHEMICAL JOURNAL, PUBLISHED BY PORTLAND PRESS ON BEHALF OF THE BIOCHEMICAL SOCIETY, vol. 366, 1 January 2002 (2002-01-01), pages 273 - 279, XP002995915, ISSN: 0264-6021
ref_type: npl
severity: background
ref_id: - ELLIOTT D A ET AL: "Isoform-specific proteolysis of apolipoprotein-E in the brain", NEUROBIOLOGY OF AGING, TARRYTOWN, NY, US, vol. 32, no. 2, 1 February 2011 (2011-02-01), pages 257 - 271, XP027544446, ISSN: 0197-4580, [retrieved on 20090310]
ref_type: npl
severity: background
ref_id: - AIZAWA Y ET AL: "AMINO-TERMINUS TRUNCATED APOLIPOPROTEIN E IS THE MAJOR SPECIES IN AMYLOID DEPOSITS IN ALZHEIMER'S DISEASE-AFFECTED BRAINS: A POSSIBLE ROLE FOR APOLIPOPROTEIN E IN ALZHEIMER'S DISEASE", BRAIN RESEARCH, ELSEVIER, AMSTERDAM, NL, vol. 768, no. 1/02, 1 January 1997 (1997-01-01), pages 208 - 214, XP008046268, ISSN: 0006-8993, DOI: 10.1016/S0006-8993(97)00640-9
ref_type: npl
severity: background
ref_id: US2017218058
ref_type: patent
severity: obviousness
ref_id: - BENTLEY N M ET AL, "Apolipoprotein E structural requirements for the formation of SDS-stable complexes with beta-amyloid-(1-40): the role of salt bridges", BIOCHEMICAL JOURNAL, PUBLISHED BY PORTLAND PRESS ON BEHALF OF THE BIOCHEMICAL SOCIETY, (20020101), vol. 366, ISSN 0264-6021, pages 273 - 279, XP002995915 [X] 1,2 * page  274, column  r, paragraph  2 * [I] 3-15
ref_type: npl
severity: novelty_destroying
ref_id: - ELLIOTT D A ET AL, "Isoform-specific proteolysis of apolipoprotein-E in the brain", NEUROBIOLOGY OF AGING, TARRYTOWN, NY, US, vol. 32, no. 2, ISSN 0197-4580, (20110201), pages 257 - 271, (20090310), XP027544446 [Y] 1-15 * In particular, Item 3 *
ref_type: npl
severity: obviousness
ref_id: - AIZAWA Y ET AL, "AMINO-TERMINUS TRUNCATED APOLIPOPROTEIN E IS THE MAJOR SPECIES IN AMYLOID DEPOSITS IN ALZHEIMER'S DISEASE-AFFECTED BRAINS: A POSSIBLE ROLE FOR APOLIPOPROTEIN E IN ALZHEIMER'S DISEASE", BRAIN RESEARCH, ELSEVIER, AMSTERDAM, NL, (19970101), vol. 768, no. 1/02, doi:10.1016/S0006-8993(97)00640-9, ISSN 0006-8993, pages 208 - 214, XP008046268 [Y] 1-15 * the whole document *
ref_type: npl
severity: obviousness
Final disposition: pending (2020-12-30)