# US 7,608,586 B2 · Soluble low-density lipoprotein receptor related protein binds directly to Alzheimer's amyloid-beta peptide > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,608,586 B2 - Document ID: US7608586B2 - Status: Granted - Kind: B2 - Application number: 10/558,984 - Filed: 2004-06-14 - Published: 2007-03-08 - Granted: 2009-10-27 - Earliest claimed: 2003-06-11 - Assignees: University of Rochester; Socratech L.L.C. - Inventors: Berislav V. Zlokovic; Rashid Deane - Web page: https://patentgrep.com/patent/US7608586B2 ## CPC - G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease} - C07K 14/4711: {Alzheimer's disease; Amyloid plaque core protein} - C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} - G01N 33/92: involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - G01N 2800/2821: Alzheimer - 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 soluble derivative of low-density lipoprotein receptor related protein-1 (sLRP-1) binds directly to Alzheimer's amyloid-β peptide (Aβ). This binding may be used to detect Aβ or to separate Aβ from the rest of a subject's body. In Alzheimer's disease, it may be used to provide diagnostic results by detecting Aβ, treatment by removing Aβ, or both. ## Claims ### Claim 1 A method of binding amyloid-β peptide (Aβ) in a body fluid and/or tissue of a subject, said method comprising: (a) providing a soluble derivative of low-density lipoprotein receptor related protein-1 (LRP-1), wherein said soluble LRP-1 derivative is comprised of cluster II, cluster IV, or both; (b) contacting said soluble LRP-1 derivative with at least said body fluid and/or tissue of said subject such that said Aβ is specifically bound; and (c) detecting said soluble LRP-1 derivative bound to Aβ. ### Claim 2 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative binds said Aβ inside said subject's body. ### Claim 3 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative binds said Aβ outside said subject's body. ### Claim 4 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative bound to Aβ is removed from said subject's body. ### Claim 5 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative bound to Aβ is inactivated such that amyloid deposits are reduced in said subject's body. ### Claim 6 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative is comprised of cluster II. ### Claim 7 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative is comprised of cluster IV. ### Claim 8 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative consists essentially of cluster II, cluster IV, or both. ### Claim 9 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative is comprised of at least one domain which mediates secretion. ### Claim 10 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative is not comprised of a domain which mediates attachment to a lipid bilayer. ### Claim 11 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative is reversibly attached to a solid substrate. ### Claim 12 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative is irreversibly attached to a solid substrate. ### Claim 13 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative is derived from human. ### Claim 14 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative does not elicit an immune response in a human. ### Claim 15 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative further comprises at least one heterologous domain. ### Claim 16 (depends on 15) The method of claim 15, wherein at least one detectable label is covalently attached to heterologous domain. ### Claim 17 (depends on 1) The method of claim 1, wherein at least one detectable label is covalently attached to said soluble LRP-1 derivative. ### Claim 18 (depends on 1) The method of claim 1, wherein said soluble LRP-1 derivative is comprised of both cluster II and cluster IV. ### Claim 19 A method of binding amyioid-β peptide (Aβ) in a body fluid of a human subject, said method comprising: (a) providing a soluble fragment of low-density lipoprotein receptor related protein-1 (LRP-1) comprising cluster II, cluster IV, or both of human LRP-1; (b) contacting said soluble fragment of LRP-1 with at least said body fluid of said human subject such that said Aβ is specifically bound; and (c) detecting said soluble fragment of LRP-1 bound to Aβ. ### Claim 20 (depends on 19) The method of claim 19, wherein said soluble fragment of LRP-1 bound to Aβ is removed from said human subject's body. ### Claim 21 (depends on 19) The method of claim 19, wherein said soluble fragment of LRP-1 bound to Aβ is inactivated such that amyloid deposits are reduced in said human subject's body. ### Claim 22 A method of binding amyloid-β peptide (Aβ) in a body fluid and/or tissue of a subject, said method comprising: (a) providing a soluble derivative of low-density lipoprotein receptor related protein-1 (LRP-1), wherein said soluble LRP-1 derivative is comprised of cluster II, cluster IV, or both; (b) contacting said soluble LRP-1 derivative with at least said body fluid and/or tissue of said subject such that said Aβ is specifically bound; and (c) removing said soluble LRP-1 derivative bound to Aβ from said subject's body. ### Claim 23 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative binds said Aβ inside said subject's body. ### Claim 24 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative binds said Aβ outside said subject's body. ### Claim 25 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative bound to Aβ is inactivated such that amyloid deposits are reduced in said subject's body. ### Claim 26 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative is comprised of cluster lI. ### Claim 27 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative is comprised of cluster IV. ### Claim 28 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative consists essentially of cluster II, cluster IV, or both. ### Claim 29 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative is comprised of at least one domain which mediates secretion. ### Claim 30 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative is not comprised of a domain which mediates attachment to a lipid bilayer. ### Claim 31 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative is reversibly attached to a solid substrate. ### Claim 32 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative is irreversibly attached to a solid substrate. ### Claim 33 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative is derived from human. ### Claim 34 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative does not elicit an immune response in a human. ### Claim 35 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative further comprises at least one heterologous domain. ### Claim 36 (depends on 35) The method of claim 35, wherein at least one detectable label is covalently attached to said heterologous domain. ### Claim 37 (depends on 22) The method of claim 22, wherein at least one detectable label is covalently attached to said soluble LRP-1 derivative. ### Claim 38 (depends on 22) The method of claim 22, wherein said soluble LRP-1 derivative is comprised of both cluster II and cluster IV. ### Claim 39 A method of binding amyloid-β peptide (Aβ) in a body fluid of a human subject, said method comprising: (a) providing a soluble fragment of low-density lipoprotein receptor related protein-1 (LRP-1) comprising cluster II, cluster IV, or both of human LRP-1; (b) contacting said soluble fragment of LRP-1 with at least said body fluid of said human subject such that said Aβ is specifically bound; and (c) removing said soluble fragment of LRP-1 derivative bound to Aβ from said subject's body. ### Claim 40 (depends on 39) The method of claim 39, wherein said soluble fragment of LRP-1 derivative bound to Aβ is inactivated such that amyloid deposits are reduced in said human subject's body.