# US 7,612,179 B2 · antibodies binding to a C-terminal fragment of apoliopoprotein E > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,612,179 B2 - Document ID: US7612179B2 - Status: Granted - Kind: B2 - Application number: 10/579,445 - Filed: 2004-11-26 - Published: 2007-05-10 - Granted: 2009-11-03 - Earliest claimed: 2003-11-28 - Assignees: AstraZeneca AB; Dyax Corp. - Inventors: Christer Nordstedt; Tom Goldschmidt; Maria Henderikx; René Hoet; Henricus Hoogenboom; Simon Hufton; Christin V. Andersson; Johanna Lindquist; Dan Sunnemark; Sergy Leonov - Web page: https://patentgrep.com/patent/US7612179B2 ## CPC - G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease} - C07K 16/18: against material from animals or humans - G01N 33/57557: {of other specific parts of the body, e.g. brain} - G01N 33/6893: {related to diseases not provided for elsewhere} - G01N 33/92: involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} - A61K 2039/505: {comprising antibodies} - C07K 2317/21: from primates, e.g. man - C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C07K 2317/52: Constant or Fc region; Isotype - C07K 2317/55: Fab or Fab' - C07K 2317/565: Complementarity determining region [CDR] - C07K 2319/00: Fusion polypeptide - G01N 2800/042: Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism - G01N 2800/2821: Alzheimer - G01N 2800/2828: Prion diseases - G01N 2800/2835: Movement disorders, e.g. Parkinson, Huntington, Tourette - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract A human antibody fragment, which antibody or fragment: (i) binds to a polypeptide having the amino acid sequence shown in SEQ ID NO: 1 of the C-terminal domain of Apolipoprotein E (ApoE-CTD) or the amino acid sequence of a part thereof; and (ii) binds to human plaques. ## Claims ### Claim 1 An isolated human, humanised or chimeric antibody or antibody fragment, which antibody or fragment: (i) binds to a polypeptide having the amino acid sequence shown in SEQ ID NO: 1 of the C-terminal domain of Apolipoprotein E (ApoE-CTD) or the amino acid sequence of a part thereof; (ii) binds to human plaques; and (iii) comprises: (a) a heavy chain CDR3 region comprising the sequence shown in SEQ ID NO: 26, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, or SEQ ID NO: 512; (b) a heavy chain CDR2 region comprising the sequence shown in SEQ ID NO: 25; (c) a heavy chain CDR1 region comprising the sequence shown in SEQ ID NO: 24; (d) a light chain CDR3 region comprising the sequence shown in SEQ ID NO: 35; (e) a light chain CDR2 region comprising the sequence shown in SEQ ID NO: 34; and (f) a light chain CDR1 region comprising the sequence shown in SEQ ID NO: 33. ### Claim 2 (depends on 1) An antibody or antibody fragment according to claim 1, wherein said heavy chain CDR3 region comprises an affinity matured variant of SEQ ID NO: 26 having the sequence shown in SEQ ID NO: 512. ### Claim 3 (depends on 1) An antibody or antibody fragment according to claim 1, wherein said heavy chain CDR3 region comprises an affinity matured variant of SEQ ID NO: 26 having the sequence shown in SEQ ID NO: 20. ### Claim 4 (depends on 1) An antibody or antibody fragment according to claim 1 wherein said heavy chain CDR3 region comprises the sequence shown in SEQ ID NO: 23. ### Claim 5 (depends on 2) An antibody or antibody fragment according to claim 2 wherein said heavy chain CDR3 region comprises an affinity matured variant of SEQ ID NO: 26 having the sequence shown in SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209 or SEQ ID NO: 210. ### Claim 6 (depends on 5) An antibody or antibody fragment according to claim 5, wherein said heavy chain CDR3 region comprises an affinity matured variant of SEQ ID NO: 26 having the sequence shown in SEQ ID NO: 207, SEQ ID NO: 208 or SEQ ID NO: 209. ### Claim 7 (depends on 1) An antibody or antibody fragment according to claim 1, wherein said polypeptide having the amino acid sequence of a part of SEQ ID NO: 1 comprises the sequence shown in SEQ ID NO: 5. ### Claim 8 (depends on 1) An antibody or antibody fragment according to claim 1, wherein said ApoE-CTD polypeptide is a recombinant polypeptide. ### Claim 9 (depends on 8) An antibody or antibody fragment according to claim 8 wherein said recombinant polypeptide is biotinylated. ### Claim 10 (depends on 1) An antibody or antibody fragment according to claim 1, which binds to said plaques in the presence of VLDL. ### Claim 11 (depends on 1) An antibody or antibody fragment according to claim 1, wherein said VLDL is present in human plasma. ### Claim 12 (depends on 11) An antibody or antibody fragment according to claim 11, which binds to the plaques in the presence of 25% plasma. ### Claim 13 (depends on 12) An antibody or antibody fragment according to claim 12, which binds to the plagues in the presence of from 25% to 50% plasma. ### Claim 14 (depends on 13) An antibody or antibody fragment according to claim 13, which binds to the plaques in the presence of 50% plasma. ### Claim 15 An isolated antibody or antibody fragment which comprises: (a) the heavy chain sequence shown in SEQ ID NO: 40 and the light chain sequence shown in SEQ ID NO: 518 and/or 519 or (b) the heavy chain sequence shown in SEQ ID NO: 40 and the light chain sequence shown in SEQ ID NO: 520 and/or 521. ### Claim 16 An isolated antibody or antibody fragment which comprises: (a) the heavy chain CDR1 sequence shown in SEQ ID NO: 24, the heavy chain CDR2 sequence shown in SEQ ID NO: 25 and the heavy chain CDR3 sequence shown in any one of SEQ ID NOS: 207, 209 and 210; and (b) the light chain ODR1, CDR2 and CDR3 sequences shown in SEQ ID NOS: 33, 34 and 35, SEQ ID NOS: 219, 247 and 269, SEQ ID NOS: 226, 252 and 275 or SEQ ID NOS: 218, 34 and 268. ### Claim 17 (depends on 16) An antibody or antibody fragment according to claim 16 wherein the heavy chain CDR3 region comprises the sequence shown in SEQ ID NO: 210 and the light chain comprises the sequences shown in SEQ ID NOS: 33, 34 and 35, the heavy chain CDR3 region comprises the sequence shown in SEQ ID NO: 209 and the light chain comprises the sequences shown in SEQ ID NOS: 219, 247 and 269 or SEQ ID NOS: 218, 34 and 268, or the heavy chain CDR3 region comprises the sequence shown in SEQ ID NO: 207 and the light chain comprises the sequence shown in SEQ ID NOS: 226, 252 and 275. ### Claim 18 (depends on 16) An antibody or antibody fragment according to claim 16, wherein the heavy chain comprises the sequence shown in any one of SEQ ID NO: 317, 318 or 319. ### Claim 19 (depends on 16) An antibody or antibody fragment according to claim 16, wherein the light chain comprises the sequence shown in SEQ ID NO: 43, 295, 294 or 304. ### Claim 20 (depends on 1) An antibody or antibody fragment according to claim 1, wherein said antibody is an lgG. ### Claim 21 (depends on 1) An antibody or antibody fragment according to claim 1, wherein said antibody fragment is a Fab fragment or scFv. ### Claim 22 (depends on 1) An antibody or antibody fragment according to claim 1, which is a monoclonal antibody. ### Claim 23 (depends on 1) An antibody or antibody fragment according to claim 1, which is a humanised antibody. ### Claim 24 (depends on 1) An antibody or antibody fragment according to claim 1, which is chimeric. ### Claim 25 (depends on 1) A pharmaceutical composition comprising an antibody or antibody fragment according to claim 1 and a pharmaceutically acceptable carrier or diluent. ### Claim 26 (depends on 1) A kit for detecting ApoE-CTD, which kit comprises an antibody or antibody fragment according to claim 1 and means for detecting said an antibody or antibody fragment. ### Claim 27 (depends on 1) An antibody or antibody fragment according to claim 1, which is a human antibody.