Hybrid amyloid-beta antibodies

• US 9,067,981 B1
• Filed: 10/29/2009
• Issued: 06/30/2015
• Est. Priority Date: 10/30/2008
• Status: Expired due to Fees

• Current Assignee: Janssen Sciences Ireland UC (Johnson & Johnson), Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Original Assignee: Janssen Sciences Ireland UC (Johnson & Johnson), Wyeth LLC (Pfizer Inc.), Board of Trustees of the Leland Stanford Junior University (Stanford University)
• Inventors: Basi, Guriqbal, Schenk, Dale B., Feinberg, Hadar Hana, Weis, William I.
• Primary Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US12/608,869
• Time in Patent Office: 2,070 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2299/00 Coordinates from 3D structures of peptides, e.g. proteins or enzymes
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/60 characterized by non-natural combinations of immunoglobulin fragments

Abstract

The present invention provides crystals including amino acids 1-7 of SEQ ID NO:1 and a Fab fragment of 12A11, 12B4, 10D5 or 3D6, as well as of amino acids 1-40 of SEQ ID NO:1 and a Fab fragment of 12A11 or 3D6, as well as methods for preparing the crystals. The present invention also provides a computer implemented method for analyzing binding of a candidate antibody fragment to a peptide including an epitope of amino acids 1-7 of SEQ ID NO:1, a method for identifying an antibody fragment that can mimic the Fab fragment of 12A11, a method for identifying an antibody fragment that can mimic the Fab fragment of 3D6, a method for identifying a candidate antibody fragment that binds to a peptide including an epitope of amino acids 1-7 of SEQ ID NO:1, and a method for designing a humanized antibody that binds to a peptide comprising an epitope of amino acids 1-7 of SEQ ID NO:1.

Claims

1. An isolated antibody that binds to an epitope within residues 3-7 of Aβ

, wherein CDRs L1, L2 and L3 are CDRs L1, L2 and L3 of an antibody other than 12A11 that binds to an epitope within residues 3-7 of Aβ

, and CDRs H1 and H2 are CDRs H1 and H2 of the antibody other than 12A11 and CDRs L1, L2, L3, H1 and H2 of the isolated antibody differ from corresponding CDRs of 12A11 and CDR H3 is either CDR H3 of antibody 12A11 or CDR H3 of the antibody other than 12A11 modified by absence of residues X2, X3 and X4 of SEQ ID NO;

28, wherein CDRs L1, L2 and L3 are CDRs L1, L2 and L3 of antibody PFA1, and CDRs H1 and H2 are CDRs H1 and H2 of antibody PFA1 and CDR H3 is CDR H3 of antibody 12A11.

2. An isolated antibody that binds to an epitope within residues 3-7 of Aβ

, wherein CDRs L1, L2 and L3 are CDRs L1, L2 and L3 of an antibody other than 12A11 that binds to an epitope within residues 3-7 of Aβ

, and CDRs H1 and H2 are CDRs H1 and H2 of the antibody other than 12A11 and CDRs L1, L2, L3, H1 and H2 of the isolated antibody differ from corresponding CDRs of 12A11 and CDR H3 is either CDR H3 of antibody 12A11 or CDR H3 of the antibody other than 12A11 modified by absence of residues X2, X3 and X4 of SEQ ID NO;

28, wherein CDRs L1, L2 and L3 are CDRs L1, L2 and L3 of antibody PFA2, and CDRs H1 and H2 are CDRs H1 and H2 of antibody PFA2 and CDR H3 is CDR H3 of antibody 12A11.