Therapeutic agent for cachexia

• US 7,468,184 B2
• Filed: 01/08/2003
• Issued: 12/23/2008
• Est. Priority Date: 05/15/1997
• Status: Expired due to Fees

• Current Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Original Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Inventors: Sato, Koh, Tsunenari, Toshiaki, Ishii, Kimie
• Primary Examiner(s): Fetterolf; Brandon J
• Application Number:
  US10/337,981
• Publication Number:
  US 20030138424A1
• Time in Patent Office: 2,176 Days
• Field of Search: 424/9.1, 424/130.1, 424/184.1, 424/133.1, 424/138.1, 424/141.1, 424/142.1, 424/155.1
• US Class Current: 424/145.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/635 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: C07K 16/26 against hormones ; against hormone releasing or inhibiting factors
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The invention relates to a therapeutic agent for cachexia comprising, as an active ingredient, a substance capable of inhibiting the binding between a parathyroid hormone related protein (PTHrP) and a receptor thereof.

Claims

1. A method for preventing or treating at least one symptom of cachexia, comprising administering to a patient suffering from cachexia at least one humanized anti-PTHrP antibody or binding fragment thereof, wherein said humanized anti-PTHrP antibody or binding fragment thereof:

a) is humanized FERM BP-5631;

b) comprises a heavy chain variable region comprising amino acids 31-35, 50-66, and 99-107 of SEQ ID NO;

46 and a light chain variable region comprising amino acids 23-34, 50-60, and 93-105 of SEQ ID NO;

45;

or

c) comprises a deletion, replacement, addition, or insertion of from 1-5 amino acid residues of humanized FERM BP-5631;

and wherein said humanized anti-PTHrP antibody or binding fragment thereof binds PTHrP.

2. The method according to claim 1, wherein the cachexia is cancer-induced.

3. The method according to claim 1, wherein said at least one symptom is chosen from at least one of anorexia, loss of appetite, weakness, anemia, compromised immune function, and electrolyte imbalance.

4. The method according to claim 1, wherein said at least one humanized anti-PTHrP antibody or binding fragment thereof is an antagonist of a PTHrP receptor.

5. The method according to claim 1, wherein said at least one humanized anti-PTHrP antibody binding fragment is Fab, scFv, F(ab'"'"')2, or Fv.

6. The method according to claim 1, wherein said humanized antibody is humanized FERM BP-5631.

7. The method according to claim 1, wherein said cachexia is mediated by at least one cytokine.

8. The method according to claim 7, wherein the cytokine is at least one of TNF, IL-6, IFN, IL-1 or LIF.

9. The method according to claim 7, wherein the cytokine is an inflammatory cytokine.

10. The method according to claim 1, wherein the humanized anti-PTHrP antibody or binding fragment thereof comprises a heavy chain variable region comprising amino acids 31-35, 50-66, and 99-107 of SEQ ID NO:

46 and a light chain variable region comprising amino acids 23-34, 50-60, and 93-105 of SEQ ID NO;

45.