公开(公告)号：US11779664B2

公开(公告)日：2023-10-10

申请号：US17737928

申请日：2022-05-05

Applicant: Texas Children's Hospital ,  Alzeca Biosciences, LLC

Inventor： Eric A. Tanifum ,  Xianwei Sun ,  Ananth V. Annapragada ,  Carlo Medici

IPC: A61K9/00 ,  A61K49/08 ,  C07C49/755 ,  C07C65/40 ,  C07D333/22 ,  A61K49/18 ,  A61K47/54 ,  A61K9/127 ,  A61K49/10

CPC classification number: A61K49/085 ,  A61K9/1271 ,  A61K47/542 ,  A61K47/544 ,  A61K47/545 ,  A61K49/108 ,  A61K49/1812 ,  C07C49/755 ,  C07C65/40 ,  C07D333/22

Abstract: A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I:




wherein X is —CH2—, —CH2—CH2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or





A and B are independently selected from C and N; R1, R2, R3, and R4 are independently selected from —H, halogen, —OH, and —CH3; and R5, R6, and R7 are independently selected from —H, halogen, —OH, —OCH3, —NO2, —N(CH3)2, C1-C6 alkyl, or a substituted or unsubstituted C4-C6 aryl group, except that when A and/or B is N the adjacent R5 and/or R7 is —H, or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20230398238A1

公开(公告)日：2023-12-14

申请号：US18455407

申请日：2023-08-24

Applicant: Texas Children's Hospital ,  Alzeca Biosciences, LLC

Inventor： Eric A. Tanifum ,  Xianwei Sun ,  Ananth V. Annapragada ,  Carlo Medici

IPC: A61K49/08 ,  C07C49/755 ,  C07C65/40 ,  C07D333/22 ,  A61K49/18 ,  A61K47/54 ,  A61K9/127 ,  A61K49/10

CPC classification number: A61K49/085 ,  C07C49/755 ,  C07C65/40 ,  C07D333/22 ,  A61K49/1812 ,  A61K47/542 ,  A61K47/545 ,  A61K9/1271 ,  A61K49/108 ,  A61K47/544

Abstract: A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I:




wherein X is —CH2—, —CH2—CH2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or




A and B are independently selected from C and N; R1, R2, R3, and R4 are independently selected from —H, halogen, —OH, and —CH3; and R5, R6, and R7 are independently selected from —H, halogen, —OH, —OCH3, —NO2, —N(CH3)2, C1-C6 alkyl, or a substituted or unsubstituted C4-C6 aryl group, except that when A and/or B is N the adjacent R5 and/or R7 is —H, or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20230136718A1

公开(公告)日：2023-05-04

申请号：US18055100

申请日：2022-11-14

Applicant: Alzeca Biosciences, LLC

Inventor： Ananth V. Annapragada ,  Peter Nilsson ,  Carlo Medici ,  Eric A. Tanifum

IPC: A61K49/12 ,  A61K9/127

Abstract: Phospholipid-polymer-aromatic conjugates comprising binding ligands, liposome compositions including the phospholipid-polymer-aromatic conjugates, and binding ligands having an affinity for misfolded proteins are described. The phospholipid-polymer-aromatic conjugate may be represented by Structural Formula I: PL-AL-HP-X-BL (I). In Formula I, PL is a phospholipid, AL is an aliphatic linkage, HP is hydrophilic polymer, X is a link between the phospholipid-polymer and the binding ligand, and BL is polycyclic aromatic compound that functions as a binding ligand. The liposomal compositions may be useful for the imaging of misfolded and/or aggregated proteins.

公开(公告)号：US20220283187A1

公开(公告)日：2022-09-08

申请号：US17739031

申请日：2022-05-06

Applicant: Alzeca Biosciences, LLC ,  Texas Children's Hospital

Inventor： Ananth Annapragada ,  Qingshan Mu ,  Carlo Medici

IPC: G01N33/68 ,  C12N15/10 ,  C12N15/115 ,  C12N15/11

Abstract: Methods and compositions for detecting tau pathology are described. The compositions for detecting tau pathology comprise a targeting ligand that specifically binds to a cell surface marker of tau pathology, wherein the targeting ligand is linked to a liposome that includes an imaging agent. The compositions can be used in a method for imaging tau pathology in a subject that comprises administering to the subject an effective amount of the composition to a subject and imaging at least a portion of the subject to determine if that portion of the subject exhibits tau pathology. The compositions can also be used to detect tau pathology in biological samples obtained from a subject.

公开(公告)号：US20180043039A1

公开(公告)日：2018-02-15

申请号：US15797816

申请日：2017-10-30

Applicant: BOARD OF REGENTS OF THE UNIVERSITY OF HOUSTON SYSTEM ,  BOARD OF REGENTS OF THE UNIVERSITY OF TEXAS SYSTEM ,  ALZECA BIOSCIENCES, LLC

Inventor： Ananth V. Annapragada ,  Jason L. Eriksen ,  Eric A. Tanifum ,  Indrani Dasgupta ,  Stephen C. Cook

IPC: A61K49/18 ,  C08G65/335 ,  A61K9/127

CPC classification number: A61K49/1812 ,  A61K9/1273 ,  A61K47/6911 ,  A61K49/0466 ,  C08G65/3353

Abstract: Lipid-based nanoparticle compositions are provided. The compositions generally comprise lipid-hydrophilic polymer-amyloid binding ligand conjugates, and may be liposomal compositions. The compositions, including the liposomal compositions, may be useful for imaging and/or the treatment of amyloid-β plaque deposits characteristic of Alzheimer's Disease.

公开(公告)号：US20210252170A1

公开(公告)日：2021-08-19

申请号：US17175359

申请日：2021-02-12

Applicant: Texas Children's Hospital ,  Alzeca Biosciences, LLC

Inventor： Eric A. Tanifum ,  Xianwei Sun ,  Ananth V. Annapragada ,  Carlo Medici

IPC: A61K49/10 ,  C07C49/577 ,  C07C65/40 ,  C07D333/22 ,  A61K49/18 ,  A61K47/60 ,  A61K49/08 ,  A61K47/54

Abstract: A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I: wherein X is —CH2—, —CH2—CH2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or A and B are independently selected from C and N; R1, R2, R3, and R4 are independently selected from —H, halogen, —OH, and —CH3; and R5, R6, and R7 are independently selected from —H, halogen, —OH, —OCH3, —NO2, —N(CH3)2, C1-C6 alkyl, or a substituted or unsubstituted C4-C6 aryl group, except that when A and/or B is N the adjacent R5 and/or R7 is —H, or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20200261605A1

公开(公告)日：2020-08-20

申请号：US16751943

申请日：2020-01-24

Applicant: ALZECA BIOSCIENCES, LLC

Inventor： Ananth V. ANNAPRAGADA ,  Peter NILSSON ,  Carlo MEDICI ,  Eric A. TANIFUM

IPC: A61K49/12 ,  A61K9/127

Abstract: Phospholipid-polymer-aromatic conjugates comprising binding ligands, liposome compositions including the phospholipid-polymer-aromatic conjugates, and binding ligands having an affinity for misfolded proteins are described. The phospholipid-polymer-aromatic conjugate may be represented by Structural Formula I: PL-AL-HP-X-BL (I). In Formula I, PL is a phospholipid, AL is an aliphatic linkage, HP is hydrophilic polymer, X is a link between the phospholipid-polymer and the binding ligand, and BL is polycyclic aromatic compound that functions as a binding ligand. The liposomal compositions may be useful for the imaging of misfolded and/or aggregated proteins.

公开(公告)号：US11614451B2

公开(公告)日：2023-03-28

申请号：US17739031

申请日：2022-05-06

Applicant: Alzeca Biosciences, LLC ,  Texas Children's Hospital

Inventor： Ananth Annapragada ,  Qingshan Mu ,  Carlo Medici

IPC: G01N33/68 ,  C12N15/10 ,  C12N15/115 ,  C12N15/11 ,  A61B5/055

Abstract: Methods and compositions for detecting tau pathology are described. The compositions for detecting tau pathology comprise a targeting ligand that specifically binds to a cell surface marker of tau pathology, wherein the targeting ligand is linked to a liposome that includes an imaging agent. The compositions can be used in a method for imaging tau pathology in a subject that comprises administering to the subject an effective amount of the composition to a subject and imaging at least a portion of the subject to determine if that portion of the subject exhibits tau pathology. The compositions can also be used to detect tau pathology in biological samples obtained from a subject.

公开(公告)号：US20220265868A1

公开(公告)日：2022-08-25

申请号：US17737928

申请日：2022-05-05

Applicant: Texas Children's Hospital ,  Alzeca Biosciences, LLC

Inventor： Eric A. Tanifum ,  Xianwei Sun ,  Ananth V. Annapragada ,  Carlo Medici

IPC: A61K49/08 ,  C07C49/755 ,  C07C65/40 ,  C07D333/22 ,  A61K47/54 ,  A61K9/127 ,  A61K49/10 ,  A61K49/18

Abstract: A liposomal composition (“ADx-003”) is provided, ADx-003 comprising a first phospholipid; a sterically bulky excipient that is capable of stabilizing the liposomal composition; a second phospholipid that is derivatized with a first polymer; a macrocyclic gadolinium-based imaging agent; and a third phospholipid that is derivatized with a second polymer, the second polymer being conjugated to a targeting ligand, the targeting ligand being represented by Formula I: wherein X is —CH2—, —CH2—CH2—, —CHO—, or —O—CO—; Y is —CH—CH═CH— or A and B are independently selected from C and N; R1, R2, R3, and R4 are independently selected from —H, halogen, —OH, and —CH3; and R5, R6, and R7 are independently selected from —H, halogen, —OH, —OCH3, —NO2, —N(CH3)2, C1-C6 alkyl, or a substituted or unsubstituted C4-C6 aryl group, except that when A and/or B is N the adjacent R5 and/or R7 is —H, or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20210128755A1

公开(公告)日：2021-05-06

申请号：US16922762

申请日：2020-07-07

Applicant: Alzeca Biosciences, LLC ,  Texas Children's Hospital

Inventor： Ananth Annapragada ,  Qingshan Mu ,  Carlo Medici

IPC: A61K49/18 ,  A61K49/08 ,  C12N15/115

Abstract: Methods and compositions for detecting tau pathology are described. The compositions for detecting tau pathology comprise a targeting ligand that specifically binds to a cell surface marker of tau pathology, wherein the targeting ligand is linked to a liposome that includes an imaging agent. The compositions can be used in a method for imaging tau pathology in a subject that comprises administering to the subject an effective amount of the composition to a subject and imaging at least a portion of the subject to determine if that portion of the subject exhibits tau pathology. The compositions can also be used to detect tau pathology in biological samples obtained from a subject.