Method for Delivering Drug to Muscle

Patent metadata

Field	Value
Publication number	US-2024245797-A1
Application number	US-202418599591-A
Country	US
Kind code	A1
Filing date	Mar 8, 2024
Priority date	Feb 5, 2018
Publication date	Jul 25, 2024
Grant date	—

Abstract

[Problems] To provide a technique for efficiently incorporating an agent having to function in muscle tissue, which is not sufficiently incorporated into muscle tissue when administered in body, into muscle tissue, particularly muscle tissue composed of skeletal muscle or cardiac muscle. [Solution] A conjugate of an anti-human transferrin receptor antibody and an agent, wherein the agent is a biologically active agent that should function in muscle tissue, e.g., a lysosomal enzyme such as acid α-glucosidase, α-galactosidase A.

First claim

1 - 47 . (canceled)

48 . A method of ameliorating muscle dysfunction in a subject, wherein the method comprising administering a pharmaceutical composition containing a conjugate of an anti-human transferrin receptor antibody and an agent, wherein the agent has a physiological activity to be exerted in muscle.

49 . The method according to claim 48 , wherein the antibody comprises the amino acid sequence set forth as SEQ ID NO: 22 in the variable region of the light chain and the amino acid sequence set forth as SEQ ID NO: 23 in the variable region of the heavy chain.

50 . The method according to claim 48 , wherein the amino acid sequence of the variable region of the light chain of the antibody has an identity not lower than 80% to the amino acid sequence set forth as SEQ ID NO: 22, and the amino acid sequence of the variable region of the heavy chain of the antibody has an identity not lower than 80% to the amino acid sequence set forth as SEQ ID NO: 23.

51 . The method according to claim 48 , wherein the amino acid sequence of the variable region of the light chain of the antibody has an identity not lower than 90% to the amino acid sequence set forth as SEQ ID NO: 22, and the amino acid sequence of the variable region of the heavy chain of the antibody has an identity not lower than 90% to the amino acid sequence set forth as SEQ ID NO: 23.

52 . The method according to claim 48 , wherein the conjugate is selected from the group consisting of (1) to (4) below:
(1) a conjugate in which the protein is linked to the C-terminal side of the light chain of the anti-human transferrin receptor antibody by a peptide bond, (2) a conjugate in which the protein is linked to the N-terminal side of the light chain of the anti-human transferrin receptor antibody by a peptide bond, (3) a conjugate in which the protein is linked to the C-terminal side of the heavy chain of the anti-human transferrin receptor antibody by a peptide bond, and (4) a conjugate in which the protein is linked to the N-terminal side of the heavy chain of the anti-human transferrin receptor antibody by a peptide bond.

53 . The method according to claim 48 , wherein the agent is a lysosomal enzyme.

54 . The method according to claim 53 , wherein the lysosomal enzyme is human acid a-glucosidase.

55 . The method according to claim 54 , wherein the muscle dysfunction is a muscle dysfunction associated with Pompe disease.

56 . The method according to claim 48 , wherein the antibody comprises the light chain variable region comprising the amino acid sequence set forth as SEQ ID NO:11 or SEQ ID NO:12 as CDR1, the amino acid sequence set forth as SEQ ID NO:13 or SEQ ID NO:14 as CDR2, and the amino acid sequence set forth as SEQ ID NO:15 as CDR3; and the heavy chain comprising the amino acid sequence set forth as SEQ ID NO:16 or SEQ ID NO:17 as CDR1, the amino acid sequence set forth as SEQ ID NO:18 or SEQ ID NO:19 as CDR2, and the amino acid sequence set forth as SEQ ID NO:20 or SEQ ID NO:21 as CDR3.

57 . The method according to claim 55 , wherein the conjugate exerts the physiological activity in a lysosome in a muscle cell.

Assignees

• Japan Chem Res

Inventors

• Takahashi Kenichi
• Sonoda Hiroyuki

Classifications

• C07K2319/33

  fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2317/14

  Specific host cells or culture conditions, e.g. components, pH or temperature · CPC title

• C07K16/2881

  against CD71 · CPC title