Patent application EP19156940A (EP), filed 2019-02-13
Publication number: EP3695883A1
Title: MEANS FOR SPECIFICALLY ELIMINATING PERILIPIN-1 FRAGMENT PRESENTING ADIPOCYTES
Abstract: [0001]    The present invention relates to an antigen-binding peptide specifically binding to at least one perilipin-1 epitope as defined herein. The present invention further relates to an antigen-binding peptide for use in the prevention or treatment of obesity. Furthermore, the present invention relates to a bispecific antigen-binding peptide comprising a first binding site specifically binding to a perilipin-1 epitope and a second binding site, and use thereof. The present invention also relates to a pharmaceutical composition, comprising an antigen-binding peptide or a bispecific antigen-binding peptide, for use in the prevention or treatment of obesity. The present invention further relates to an isolated nucleic acid encoding for an antigen-binding peptide or a bispecific antigen-binding peptide. Furthermore, the present invention relates to a recombinant cell comprising said nucleic acid and to a method of producing a means for specifically targeting perilipin-1 fragment presenting adipocytes.
IPC codes: A61P   3/    04            A I
C07K  16/    18            A I
Claims: number: 1
text: An antigen-binding peptide specifically binding to at least one perilipin-1 epitope selected from the following amino acid sequences: LTLLDGDLPE (SEQ ID NO. 1), EKIASELK (SEQ ID NO. 2), VPIASTSDKV (SEQ ID NO. 3), PAPGHQQAQK (SEQ ID NO. 4), PSLLSRVGALTN (SEQ ID NO. 5), and PWLHSLAA (SEQ ID NO. 6).
number: 2
text: The antigen-binding peptide according to claim 1, wherein antigen-binding peptide binds to more than one of SEQ ID NO. 1-6.
number: 3
text: The antigen-binding peptide according to claim 1 or 2, wherein said perilipin-1 epitope is a human perilipin-1 epitope.
number: 4
text: The antigen-binding peptide according to any of the foregoing claims, wherein said antigen-binding peptide is not a perilipin-1 targeting autoantibody of a human patient having lipoatrophy, and wherein preferably said antigen-binding peptide is not a perilipin-1 targeting anti-PLINl antibody directed to the peptide spanning Thr8-Ala145 having catalog # AF6615 from manufacturer R&D.
number: 5
text: The antigen-binding peptide according to any of the foregoing claims, wherein said antigen-binding peptide competes for binding with a perilipin-1 targeting autoantibody of a human patient having lipoatrophy.
number: 6
text: The antigen-binding peptide according to any of the foregoing claims, wherein said antigen-binding peptide binds to perilipin-1 in a binding assay with an affinity (K<D>) of at least 10<-4> M.
number: 7
text: The antigen-binding peptide according to any of the foregoing claims, wherein said antigen-binding peptide is a monoclonal antibody.
number: 8
text: The antigen-binding peptide according to any of the foregoing claims, wherein said antigen-binding peptide is a human antibody, a humanised antibody, or a chimeric-human antibody.
number: 9
text: The antigen-binding peptide according to any of the foregoing claims, wherein said antigen-binding peptide is an intact antibody, a substantially intact antibody, a Fab fragment, a F(ab')<2> fragment, or a single chain Fv fragment.
number: 10
text: The antigen-binding peptide according to any of the foregoing claims, wherein said antigen-binding peptide is capable of binding to a perilipin-1 fragment presented on an adipocyte, and wherein said binding of said antigen-binding peptide to a perilipin-1 fragment on said adipocyte activates an immune effector system to target and/or eliminate said adipocyte.
number: 11
text: The antigen-binding peptide according to any of the foregoing claims, wherein said antigen-binding peptide comprises an Fc region, preferably an Fc region which is optimized by protein engineering for higher binding affinity to an effector cell compared to a binding affinity of an Fc region which has not been optimized.
number: 12
text: The antigen-binding peptide, wherein said antigen-binding peptide does not cross-react with any other perilipin protein, such as perilipin-2 -3, -4, or -5.
number: 13
text: An antigen-binding peptide as defined in any of the foregoing claims for use in the prevention or treatment of obesity.
number: 14
text: A bispecific antigen-binding peptide comprising
number: 15
text: The bispecific antigen-binding peptide according to claim 14, wherein said second binding site binds to a perilipin-1 epitope having any of SEQ ID NO. 1-6, wherein said epitope is equal to or different from the epitope of said first binding site; to a white adipocyte-specific surface marker, for example the neutral amino acid transporter ASC-1; or to an immune cell specific receptor molecule, such as a T cell specific receptor molecule or a natural killer cell specific receptor molecule.
number: 16
text: A bispecific antigen-binding peptide according to claim 14 or 15 for use in the prevention or treatment of obesity.
number: 17
text: A pharmaceutical composition comprising the antigen-binding peptide according to any of claims 1-12, and/or the bispecific antigen-binding peptide according to any of claims 14-15, for use in the prevention or treatment of obesity.
number: 18
text: An isolated nucleic acid encoding for an antigen-binding peptide as defined in any of claims 1-12, or encoding for a bispecific antigen-binding peptide as defined in claim 14 or 15.
number: 19
text: A recombinant cell comprising a nucleic acid as defined in claim 18, wherein said recombinant cell is preferably a recombinant autologous effector cell or a recombinant host cell.
number: 20
text: A method of producing a means for specifically targeting perilipin-1 fragment presenting adipocytes, comprising:
number: 21
text: The method according to claim 20, wherein said means targets perilipin-1 and is selected from an antigen-binding peptide and a cytotoxic T cell.
Office action: search_report, dated 2020-08-19
Rejection reasons: novelty_epc_54
Prior art cited: ref_id: WO0228410A1
ref_type: patent
severity: background
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severity: background
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ref_type: npl
severity: background
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ref_type: npl
severity: background
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ref_type: npl
severity: background
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ref_type: npl
severity: background
ref_id: WO0228410A1
ref_type: patent
severity: background
ref_id: WO03019142A2
ref_type: patent
severity: background
ref_id: - GREENBERG A S ET AL: "Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associted with the periphery of lipid storage droplets", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 266, no. 17, 15 June 1991 (1991-06-15), pages 11341 - 11346, XP002973236, ISSN: 0021-9258
ref_type: npl
severity: background
ref_id: - YANXIN WANG ET AL: "Perilipin Expression in Human Adipose Tissues: Effects of Severe Obesity, Gender, and Depot", OBESITY RESEARCH., vol. 11, no. 8, 1 August 2003 (2003-08-01), US, pages 930 - 936, XP055610342, ISSN: 1071-7323, DOI: 10.1038/oby.2003.128
ref_type: npl
severity: background
ref_id: - FERNANDO CORVILLO ET AL: "Autoantibodies Against Perilipin 1 as a Cause of Acquired Generalized Lipodystrophy", FRONTIERS IN IMMUNOLOGY, vol. 9, 1 January 2018 (2018-01-01), CH, pages 2142 - 2142, XP055610271, ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.02142
ref_type: npl
severity: background
ref_id: - XIAOXIANG DENG ET AL: "Enhancing antibody patent protection using epitope mapping information", MABS, vol. 10, no. 2, 7 December 2017 (2017-12-07), US, pages 204 - 209, XP055469435, ISSN: 1942-0862, DOI: 10.1080/19420862.2017.1402998
ref_type: npl
severity: background
ref_id: - P. W. MATHIESON ET AL: "Complement-mediated adipocyte lysis by nephritic factor sera", THE JOURNAL OF EXPERIMENTAL MEDICINE, vol. 177, no. 6, 1 June 1993 (1993-06-01), US, pages 1827 - 1831, XP055610420, ISSN: 0022-1007, DOI: 10.1084/jem.177.6.1827
ref_type: npl
severity: background
ref_id: WO0228410
ref_type: patent
severity: novelty_destroying
ref_id: WO03019142
ref_type: patent
severity: background
ref_id: - GREENBERG A S ET AL, "Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associted with the periphery of lipid storage droplets", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, (19910615), vol. 266, no. 17, ISSN 0021-9258, pages 11341 - 11346, XP002973236 [X] 1-12,17-19 * page  11342, column  l, paragraph  4 * [I] 14-16,20,21
ref_type: npl
severity: novelty_destroying
ref_id: - YANXIN WANG ET AL, "Perilipin Expression in Human Adipose Tissues: Effects of Severe Obesity, Gender, and Depot", OBESITY RESEARCH., US, (20030801), vol. 11, no. 8, doi:10.1038/oby.2003.128, ISSN 1071-7323, pages 930 - 936, XP055610342 [I] 1-21 * page  931, column  r, paragraph  2 *
ref_type: npl
severity: background
ref_id: - FERNANDO CORVILLO ET AL, "Autoantibodies Against Perilipin 1 as a Cause of Acquired Generalized Lipodystrophy", FRONTIERS IN IMMUNOLOGY, CH, (20180101), vol. 9, doi:10.3389/fimmu.2018.02142, ISSN 1664-3224, pages 2142 - 2142, XP055610271 [I] 1-21 * page  11, lines  16-25; figures 3,5,7 *
ref_type: npl
severity: background
ref_id: - XIAOXIANG DENG ET AL, "Enhancing antibody patent protection using epitope mapping information", MABS, US, (20171207), vol. 10, no. 2, doi:10.1080/19420862.2017.1402998, ISSN 1942-0862, pages 204 - 209, XP055469435 [T] 1-21 * the whole document *
ref_type: npl
severity: background
ref_id: - P. W. MATHIESON ET AL, "Complement-mediated adipocyte lysis by nephritic factor sera", THE JOURNAL OF EXPERIMENTAL MEDICINE, US, (19930601), vol. 177, no. 6, doi:10.1084/jem.177.6.1827, ISSN 0022-1007, pages 1827 - 1831, XP055610420 [A] 1-21 * the whole document *
ref_type: npl
severity: background
Final disposition: pending (2020-08-19)