# US 2024/0201167 A1 · The immunomodulatory ligand b7-1 mediates synaptic remodeling by p75ntr > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2024/0201167 A1 - Document ID: US20240201167A1 - Status: Published application - Kind: A1 - Application number: 18/556,488 - Filed: 2022-04-21 - Published: 2024-06-20 - Earliest claimed: 2021-04-22 - Assignees: Albert Einstein College of Medicine - Applicants: Albert Einstein College of Medicine - Inventors: Barbara Hempstead; Francis Lee; Roshelle Smith; Victor Danelon; Steven Almo; Nicholas Morano; Sarah Garrett - Web page: https://patentgrep.com/patent/US20240201167A1 ## CPC - G01N 33/5008: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics} - A61P 25/00: Drugs for disorders of the nervous system - C07K 14/70521: {CD28, CD152} - C07K 16/2827: {against B7 molecules, e.g. CD80, CD86} - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - C07K 2319/32: fusions with soluble part of a cell surface receptor, "decoy receptors" - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract As described herein, binding of the B7-1 protein with the neuronal cell surface p75 neurotrophin receptor protein triggers loss of synaptic connections. Methods and compositions are also described for treatment of neurological diseases and conditions (including pain) and for identifying therapeutic agents useful for treatment of neurological diseases and conditions (including pain). ## Claims ### Claim 1 A method comprising incubating one or more test agents with B7-1 and p75 neurotrophin receptor and measuring whether one or more of the test agents reduces B7-1 binding to p75 neurotrophin receptor. ### Claim 2 (depends on 1) The method of claim 1, wherein one or more of the test agents is a small molecule, antibody, antibody fragment, antibody-derived construct, Fc-fusion protein, protein, peptide, aptamer, peptide aptamer, nucleic acid aptamer, darpin, nanobody, affinity reagent, liposome displaying at least one test agent, or cell expressing at least one test agent on its cell surface. ### Claim 3 (depends on 1) The method of claim 1, wherein the B7-1 or the p75 neurotrophin receptor is in soluble form. ### Claim 4 (depends on 1) The method of claim 1, wherein the B7-1 or the p75 neurotrophin receptor is fused to an Fc antibody fragment. ### Claim 5 (depends on 1) The method of claim 1, wherein the B7-1 and the p75 neurotrophin receptor are expressed separately on different cells, or at least one of B7-1 or p75 neurotrophin receptor is linked to different beads or carriers. ### Claim 6 (depends on 1) The method of claim 1, further comprising selecting one or more of the test agents that reduce B7-1 binding to p75 neurotrophin receptor by at least 25%, or at least 50%, or at least 75% compared to a control assay mixture of the B7-1 and the p75 neurotrophin receptor without the one or more test agents, to thereby identify at least one B7-1 blocking agent. ### Claim 7 (depends on 1) The method of claim 1, further comprising selecting one or more of the test agents that reduce B7-1 binding to p75 neurotrophin receptor and also reduces B7-1 binding to CD28, CTLA-4, or both. ### Claim 8 (depends on 6) The method of claim 6, further comprising incubating at least one B7-1 blocking agent with B7-1 in the presence of CD28 or CTLA-4, and measuring whether at least one of the B7-1 blocking agents reduces B7-1 binding to CD28 or CTLA-4. ### Claim 9 (depends on 8) The method of claim 8, further comprising selecting one or more of the B7-1 blocking agents that does not significantly reduce B7-1 binding to CD28 or CTLA-4 to thereby identify at least one B7-1-specific blocking agent. ### Claim 10 (depends on 9) The method of claim 9, further comprising incubating at least one B7-1-specific blocking agent in a culture comprising B7-1 and neurons that express p75 neurotrophin receptors, and measuring synaptic puncta density of the neurons that express p75 neurotrophin receptor. ### Claim 11 (depends on 10) The method of claim 10, wherein the neurons comprise dendrites. ### Claim 12 (depends on 10) The method of claim 10, further comprising selecting at least one B7-1-specific blocking agent that maintains higher levels of synaptic puncta density compared to a control culture comprising B7-1 and neurons that express p75 neurotrophin receptor without the B7-1-specific blocking agent, to thereby identify a B7-1 inhibitor. ### Claim 13 (depends on 12) The method of claim 12, further comprising administering the B7-1 inhibitor to an animal model of a neuronal condition or disease.\ ### Claim 14 (depends on 13) The method of claim 13, further comprising measuring whether the animal model has reduced symptoms of Alzheimer's disease, cognitive impairment, multiple sclerosis, stroke, neuronal injury, traumatic neural injury, spinal cord injury, pain, lupus, Parkinson's disease, anxiety, schizophrenia, manic depression, delirium, dementia, mental retardation, Huntington's disease, or Tourette's syndrome, compared to a model animal that did not receive the at least one B7-1-specific blocking agent or at least one B7-1 inhibitor. ### Claim 15 A method comprising administering abatacept or belatacept to a subject having a neuronal condition or disease to thereby treat the neuronal condition or disease. ### Claim 16 (depends on 15) The method of claim 15, wherein the subject has symptoms of Alzheimer's disease, cognitive impairment, multiple sclerosis, stroke, neuronal injury, traumatic neural injury, spinal cord injury, pain, lupus, Parkinson's disease, anxiety, schizophrenia, manic depression, delirium, dementia, mental retardation, Huntington's disease, or Tourette's syndrome. ### Claim 17 A method comprising administering a modified CTLA-4 protein that can block of B7 binding, a modified CD28 protein that can block of B7 binding, a modified Inducible T Cell Costimulator Ligand (ICOSL) protein that can block of B7 binding, or combinations thereof to a subject having a neuronal condition or disease to thereby treat the neuronal condition or disease. ### Claim at position 18 18-37. (canceled)