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US-12623013-B2 - Compounds, systems, and techniques for removal of peripheral amyloid beta peptide with albumin binding competitors

US12623013B2US 12623013 B2US12623013 B2US 12623013B2US-12623013-B2

Abstract

Compounds, systems, kits, methods, and/or apparatuses may be operative to reduce amyloid beta (Aβ) peptide in a patient, including a central nervous system (CNS) of the patient and/or a periphery (non-CNS portion) of the patient. In some embodiments, a displacer fluid comprising a Aβ displacer may be introduced to the patient to bind to a blood protein, such as albumin, that binds Aβ (for instance, Aβ peptide or non-plaque Aβ) in the patient periphery. Binding of the displacer to the blood protein may facilitate more free Aβ peptide (for instance, Aβ monomers) in the periphery for clearance via natural processes, such as through the liver or kidneys, and/or artificial processes, such as dialysis. Increased removal of the free Aβ peptide in the periphery may ultimately lead to less Aβ peptide in the CNS, which may decrease Aβ plaque formation in Alzheimer's Disease (AD) patients. Other embodiments are described.

Inventors

  • Xia Tao
  • Peter Kotanko
  • Stephan Thijssen
  • Vaibhav Maheshwari

Assignees

  • FRESENIUS MEDICAL CARE HOLDINGS, INC.

Dates

Publication Date
20260512
Application Date
20221219

Claims (9)

  1. 1 . A system, comprising: a reservoir storing a displacer fluid comprising at least one displacer, the displacer fluid configured to reduce amyloid beta (Aβ) peptide binding to albumin to increase a concentration of unbound Aβ peptide in a circulatory system of a patient, thereby increasing a clearance of Aβ peptide from a periphery of the patient, the periphery comprising at least one non-central nervous system (CNS) portion of a patient; a fluid circuit for the displacer fluid; a pump device configured to pump the displacer fluid from the reservoir and through the fluid circuit; and a control circuit configured to control the operation of the pump device to cause the flow of the displacer fluid through the fluid unit.
  2. 2 . The system of claim 1 , the fluid circuit configured to be fluidically coupled to the circulatory system of a patient.
  3. 3 . The system of claim 1 , the at least one displacer comprising one or more of an albumin binding peptide ligand (ABP) or an albumin-binding protein domain (ABD).
  4. 4 . The system of claim 1 , the system comprising a dialysis machine.
  5. 5 . The system of claim 1 , the at least one displacer comprising SA21.
  6. 6 . The system of claim 1 , the at least one displacer comprising at least one of the following: albumin-binding protein domain (ABD)035, deimmunized ABD, or ABDCon.
  7. 7 . The system of claim 1 , the at least one displacer comprising at least one of the following: anti-serum albumin domain antibodies (AlbudAbs), albumin-binding domain antibody (AlbudAb), or CA645.
  8. 8 . The system of claim 1 , wherein the reservoir further includes dialysate.
  9. 9 . The system of claim 1 , wherein the fluid circuit comprises an extracorporeal circuit for flowing the displacer fluid into patient blood.

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims the benefit to U.S. Provisional Application No. 63/293,122, filed Dec. 23, 2021, the entire contents of which are incorporated herein by reference in their entirety. FIELD The disclosure generally relates to compounds, systems, and/or techniques for increasing the removal of target substances, including amyloid beta (Aβ) (for instance, Aβ peptide), from the blood of a patient using a displacer compound. STATEMENT REGARDING A SEQUENCE LISTING The present application contains a sequence listing entitled 8142_0110_SequenceListing.xml created Jan. 27, 2026, which is 20,275 bytes in size. The sequence listing is hereby incorporated by reference in its entirety. BACKGROUND Amyloid beta (Aβ) deposition in the central nervous system (CNS) is a hallmark of Alzheimer's disease (AD). The accumulation of Aβ into oligomers and fibrils (for instance, plaques or Aβ plaques) has a key role in the neurodegenerative process and cognitive impairment of AD patients. Therapies have been tested that target Aβ, for example, via eliciting an immune response against beta-amyloid plaques, blocking/dissolving and reducing Aβ protofibril aggregation, or inhibit formation of Aβ precursors. Most conventional therapies have focused on affecting the Aβ levels in the CNS and, more particularly, the cerebrospinal fluid (CSF), with limited effectiveness. Accordingly, AD treatments may benefit from therapies that target other patient systems. It is with respect to these and other considerations that the present improvements may be useful. SUMMARY This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is not intended to necessarily identify key features or essential features of the claimed subject matter, nor is it intended as an aid in determining the scope of the claimed subject matter. In one embodiment, a system may include a reservoir storing a displacer fluid comprising at least one displacer, the displacer fluid may be configured to reduce amyloid beta (Aβ) peptide binding to a blood protein. In some embodiments, Aβ and/or Aβ peptide referred to in the present disclosure may refer to Aβ peptide or other forms of Aβ that are not in the form of plaques (for instance, plaques in the brain, central nervous system, and/or the like, that are considered to be a cause of Alzheimer's disease). In some embodiments, Aβ peptide or non-plaque Aβ may be or may include Aβ monomers and/or oligomers. In various embodiments, the system may further include a fluid circuit for the displacer fluid; a pump device configured to pump the displacer fluid from the reservoir and through the fluid circuit; and a control unit configured to control the operation of the pump device to cause the flow of the displacer fluid through the fluid circuit. In some embodiments of the system, the fluid circuit may be configured to be fluidically coupled to a circulatory system of a patient. In various embodiments of the system, the displacer fluid may be configured to increase a clearance of Aβ peptide from a periphery of the patient, the periphery comprising at least one non-central nervous system (CNS) portion of a patient. In some embodiments of the system, increasing the clearance of Aβ peptide may include increasing Aβ peptide monomers in the blood of the patient. In exemplary embodiments of the system, the blood protein may include albumin. In some embodiments of the system, the at least one displacer may include one or more of an albumin binding peptide ligand (ABP) or an albumin-binding protein domain (ABD). In various embodiments of the system, the at least one displacer may include at least one of the following: Anti-HER2, huPA inhibitor, jFXHa inhibitor, Fab, Exendin-4, G148-ABD, ABD035, ABD094, and 89D03. In some embodiments of the system, the system may include a dialysis machine. In one embodiments, a method of reducing amyloid beta Aβ peptide in a patient may include providing an Aβ displacer to the patient, the Aβ displacer configured to bind with albumin in a periphery of the patient to increase free Aβ peptide in the periphery, and removing the free Aβ peptide from the periphery. In some embodiments of the method, the Aβ displacer may be configured to increase a clearance of amyloid beta Aβ peptide from the periphery of the patient, the periphery comprising at least one non-central nervous system (CNS) portion of a patient. In various embodiments of the method, the free Aβ peptide may be removed from the periphery via a dialysis machine. In some embodiments of the method, the Aβ displacer may be provided during a dialysis treatment of the patient. In various embodiments of the method, the Aβ displacer may be provided within dialysate. In exemplary embodiments of the method, the Aβ displacer may include one or more of an albumin binding peptide ligand (ABP) or an albumin-binding protein domain (AB