# US 11,028,184 B2 · Long-acting PCSK9-specific binding protein and application thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,028,184 B2 - Document ID: US11028184B2 - Status: Granted - Kind: B2 - Application number: 16/308,811 - Filed: 2017-06-08 - Published: 2019-06-27 - Granted: 2021-06-08 - Earliest claimed: 2016-06-08 - Assignees: Changzhou Bojia Biotechnology Co., Ltd - Applicants: Changzhou Bojia Biotechnology Co., Ltd - Inventors: Shaoxiong Wang - Web page: https://patentgrep.com/patent/US11028184B2 ## CPC - C07K 16/40: against enzymes - A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum - A61P 3/06: Antihyperlipidemics - C12N 9/6424: {Serine endopeptidases (3.4.21)} - C12N 15/62: DNA sequences coding for fusion proteins - C12Y 304/21061: Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9 - G01N 33/532: Production of labelled immunochemicals - G01N 33/582: {with fluorescent label} - G01N 33/583: {with non-fluorescent dye label} - G01N 33/6893: {related to diseases not provided for elsewhere} - 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) - C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor - C07K 2317/565: Complementarity determining region [CDR] - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - G01N 2333/96433: Serine endopeptidases (3.4.21) - G01N 2800/04: Endocrine or metabolic disorders - G01N 2800/324: Coronary artery diseases, e.g. angina pectoris, myocardial infarction - G01N 2800/7066: Metabolic pathways - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - C12Y: ENZYMES - 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) ## Abstract Provided is a long-acting PCSK9-specific binding protein and application thereof. Provided is an MV072 protein with unique complementarity-determining regions, i.e., a binding protein specifically binding to proprotein convertase subtilisin kexin type 9 (PCSK9). The protein can specifically bind to PCSK9, effectively inhibit the function of PCSK9 and reduce plasma LDL cholesterol level. Further provided is an application of the binding protein in treating diseases related to or influenced by the function of PCSK9. ## Claims ### Claim 1 A binding protein MV072 that specifically binds to PCSK9, wherein the binding protein MV072 has a light chain variable region and a heavy chain variable region, and the amino acid sequence of the heavy chain variable region CDR1 thereof is set forth in SEQ ID NO: 7; the amino acid sequence of the heavy chain variable region CDR2 thereof is set forth in SEQ ID NO: 8 or SEQ ID NO: 13; the amino acid sequence of the heavy chain variable region CDR3 thereof is set forth in SEQ ID NO: 9 or SEQ ID NO: 14; the amino acid sequence of the light chain variable region CDR1 thereof is set forth in SEQ ID NO: 10; the amino acid sequence of the light chain variable region CDR2 thereof is set forth in SEQ ID NO:11; and the amino acid sequence of the light chain variable region CDR3 thereof is set forth in SEQ ID NO: 12. ### Claim 2 (depends on 1) The binding protein MV072 that specifically binds to PCSK9 according to claim 1, which is selected from the group consisting of: (a) the amino acid sequences of CDR1, CDR2 and CDR3 in the heavy chain variable region are set forth in SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, respectively; and the amino acid sequences of CDR1, CDR2 and CDR3 in the light chain variable region are set forth in SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively; or (b) the amino acid sequences of CDR1, CDR2 and CDR3 in the heavy chain variable region are set forth in SEQ ID NO: 7, SEQ ID NO: 13, and SEQ ID NO: 14, respectively; and the amino acid sequences of CDR1, CDR2 and CDR3 in the light chain variable region are set forth in SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively. ### Claim 3 (depends on 1) The binding protein MV072 that specifically binds to PCSK9 according to claim 1, wherein the amino acid sequence of the heavy chain variable region thereof is set forth in SEQ ID NO: 2 or SEQ ID NO: 24, and the amino acid sequence of the light chain variable region thereof is set forth in SEQ ID NO: 4 or SEQ ID NO: 26; or the amino acid sequence of the heavy chain variable region thereof is set forth in SEQ ID NO: 6 or SEQ ID NO: 28, and the amino acid sequence of the light chain variable region thereof is set forth in SEQ ID NO: 4 or SEQ ID NO: 26. ### Claim 4 (depends on 1) The binding protein MV072 that specifically binds to PCSK9 according to claim 1, wherein the heavy chain variable region thereof is further linked to IgG1 Fc. ### Claim 5 (depends on 4) The binding protein MV072 that specifically binds to PCSK9 according to claim 4, wherein the IgG1 Fc is: a mutant IgG1 Fc carrying T255Q and M433L mutations and having the amino acid sequence set forth in SEQ ID NO: 30; or a mutant IgG1 Fc carrying M257Y, S259T and T261E mutations and having the amino acid sequence set forth in SEQ ID NO: 32. ### Claim 6 (depends on 5) The binding protein MV072 that specifically binds to PCSK9 according to claim 5, wherein the amino acid sequence obtained by ligating the heavy chain variable region with IgG1 Fc is set forth in SEQ ID NO: 30 or SEQ ID NO: 32. ### Claim 7 (depends on 1) A pharmaceutical composition, wherein the pharmaceutical composition comprises: an effective amount of the binding protein MV072 that specifically binds to PCSK9 according to claim 1; and a pharmaceutically acceptable carrier. ### Claim 8 (depends on 1, 7) A kit for treating and/or preventing a condition associated with high serum cholesterol levels, wherein the kit comprises: the binding protein MV072 that specifically binds to PCSK9 according to claim 1 or the pharmaceutical composition according to claim 7; and instructions for administration. ### Claim 9 (depends on 1) An immunoconjugate, wherein the immunoconjugate comprises: the binding protein MV072 that specifically binds to PCSK9 according to claim 1; and a detectable label. ### Claim 10 (depends on 9) The immunoconjugate according to claim 9, wherein the detectable label comprises one or more of a fluorescent label and a chromogenic label. ### Claim 11 (depends on 1) A detection kit for detecting the level of PCSK9, wherein the detection kit comprises: the binding protein MV072 that specifically binds to PCSK9 according to claim 1; and a detection label. ### Claim 12 (depends on 9, 11) The detection kit for detecting the level of PCSK9 according to claim 11, wherein the detection kit further comprises: the immunoconjugate according to claim 9.