# US 10,865,412 B2 · Therapeutics targeting IGFBP7 for the treatment or prevention of heart failure and metabolic diseases > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,865,412 B2 - Document ID: US10865412B2 - Status: Granted - Kind: B2 - Application number: 15/803,453 - Filed: 2017-11-03 - Published: 2018-05-10 - Granted: 2020-12-15 - Earliest claimed: 2016-11-04 - Assignees: Ottawa Heart Institute Research Corporation - Applicants: Ottawa Heart Institute Research Corporation - Inventors: Peter Liu; Liyong Zhang - Web page: https://patentgrep.com/patent/US10865412B2 ## CPC - C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} - A61K 31/365: Lactones - A61K 31/713: Double-stranded nucleic acids or oligonucleotides - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - C07K 16/18: against material from animals or humans - G01N 33/5061: {Muscle cells} - G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease} - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C12N 2310/14: interfering nucleic acids [NA] - G01N 2333/4745: Insulin-like growth factor binding protein - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - 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) - 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) - 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 Insulin-like growth factor-binding protein 7 (IGFBP7) has been identified herein as a therapeutic target for the treatment or prevention of heart diseases, metabolic diseases, and other related disease or conditions. IGFBP7 inhibitors having IGFBP7 expression and/or activity reducing properties are described herein. Treatment methods, and uses, relating to such IGFBP7 inhibitors for the treatment or prevention of heart failure, IGFBP7-related metabolic diseases, and related diseases or conditions are provided. ## Claims ### Claim 1 A method for the treatment of heart failure in a subject in need thereof, said method comprising: administering an insulin-like growth factor-binding protein 7 (IGFBP7) inhibitor comprising a gene silencing nucleic acid targeting an IGFBP7 gene or an IGFBP7 mRNA in said subject to said subject to directly reduce IGFBP7 expression and/or activity levels in the heart of said subject, thereby treating heart failure in said subject. ### Claim 2 (depends on 1) The method of claim 1, additionally comprising: administering an insulin-like growth factor 1 receptor (IGF-1R) inhibitor to said subject to directly inhibit IGF-1R expression and/or activity levels in the heart of said subject, wherein the IGF-1R inhibitor is selected from a group consisting of a gene silencing nucleic acid targeting an IGF-1R gene or an IGF-1R mRNA; an anti-IGF-1R antibody and/or picropodophyllin. ### Claim 3 (depends on 1) The method of claim 1, wherein the subject is human. ### Claim 4 (depends on 1) The method of claim 1, wherein the heart failure is pressure overload induced heart failure. ### Claim 5 (depends on 1) The method of claim 1, wherein the method attenuates pressure overload induced cardiac fibrosis, fibrosis remodeling, or both, in said subject. ### Claim 6 (depends on 1) The method of claim 1, wherein the method reduces stress-induced cellular senescence in said subject. ### Claim 7 (depends on 1) The method of claim 1, wherein the method reduces cardiac hypertrophy, hypertrophic remodeling, or both, in said subject. ### Claim 8 (depends on 1) The method of claim 1, wherein the heart failure is heart failure with preserved ejection fraction (HFpEF). ### Claim 9 A method for the treatment of heart failure in a subject in need thereof, said method comprising: administering an insulin-like growth factor-binding protein 7 (IGFBP7) inhibitor comprising an anti-IGFBP7 antibody to said subject to directly reduce IGFBP7 expression and/or activity levels in the heart of said subject, thereby treating heart failure in said subject. ### Claim 10 (depends on 9) The method of claim 9, wherein the heart failure is pressure overload induced heart failure. ### Claim 11 (depends on 9) The method of claim 9, wherein the method attenuates pressure overload induced cardiac fibrosis, fibrosis remodeling, or both, in said subject. ### Claim 12 (depends on 9) The method of claim 9, wherein the method reduces stress-induced cellular senescence in said subject. ### Claim 13 (depends on 9) The method of claim 9, wherein the method reduces cardiac hypertrophy, hypertrophic remodeling, or both, in said subject. ### Claim 14 (depends on 9) The method of claim 9, wherein the heart failure is heart failure with preserved ejection fraction (HFpEF). ### Claim 15 (depends on 9) The method of claim 9, wherein the subject is human. ### Claim 16 (depends on 9) The method of claim 9, additionally comprising: administering an insulin-like growth factor 1 receptor (IGF-1R) inhibitor to said subject to directly inhibit IGF-1R expression and/or activity levels in the heart of said subject, wherein the IGF-1R inhibitor is selected from a group consisting of a gene silencing nucleic acid targeting an IGF-1R gene or an IGF-1R mRNA, an anti-IGF-1R antibody and/or picropodophyllin. ### Claim 17 A method for the treatment of heart failure in a subject in need thereof, said method comprising: administering an insulin-like growth factor-binding protein 7 (IGFBP7) inhibitor to said subject to directly reduce IGFBP7 expression and/or activity levels in the heart of said subject wherein the inhibitor is selected from a group consisting of a gene silencing nucleic acid directly targeting an IGFBP7 gene or an IGFBP7 mRNA and/or an anti-IGFBP7 antibody; and administering an insulin-like growth factor 1 receptor (IGF-1R) inhibitor comprising an anti-IGF-1R antibody to said subject to directly inhibit IGF-1R expression and/or activity levels in the heart of said subject; thereby treating heart failure in said subject.