Antibody against human parathormone related peptides

• US 6,903,194 B1
• Filed: 09/24/1997
• Issued: 06/07/2005
• Est. Priority Date: 09/26/1996
• Status: Expired due to Fees

• Current Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Original Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Inventors: Yabuta, Naohiro, Wakahara, Yuji, Sato, Koh
• Primary Examiner(s): Nickol, G.
• Assistant Examiner(s): Yaen, C.
• Application Number:
  US09/269,332
• Time in Patent Office: 2,813 Days
• Field of Search: 530/387.1, 530/388.1, 530/388.24, 530/388.85, 530/350, 530/300, 424/130.1, 424/178.1, 424/133.1, 424/134.1, 424/135.1, 424/141.1, 424/156.1, 424/158.1, 514/2
• US Class Current: 530/387.1
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

Disclosed are an antibody against human para-thyroid-hormone-related protein, a DNA coding for the antibody, a recombinant vector containing the DNA, a transformant transformed with the recombinant vector, a method for preparation of the antibody, and uses of the antibody.

Claims

1. An isolated polypeptide comprising an L chain V region of a humanized antibody comprising an amino acid sequence chosen from SEQ ID NOs:

48-51.

4. An isolated L chain of a humanized antibody which binds to a human parathyroid hormone related protein, comprising a polypeptide comprising an L chain C region of a human antibody and a polypeptide comprising an L chain V region according to claim 1 or 2.

6. An isolated humanized antibody comprising an L chain of a humanized antibody according to claim 4 and an H chain of a humanized antibody according to claim 5, wherein the humanized antibody binds to a human parathyroid hormone related protein.

7. An agent for suppressing hypercalcemia comprising the humanized antibody of claim 6 as an effective ingredient.

8. An agent for suppressing hypercalcemia associated with malignant tumor, comprising the humanized antibody of claim 6 as an effective ingredient.

9. The agent for suppressing hypercalcemia according to claim 8, wherein the malignant tumor is at least one chosen from cancer of the pancreas, lung cancer, cancer of the pharynx, cancer of the larynx, cancer of the tongue, cancer of the gingiva, cancer of the esophagus, cancer of the stomach, cancer of the biliary duct, cancer of the breast, cancer of the kidney, cancer of the urinary bladder, cancer of the uterus and prostate cancer, and malignant lymphoma.

10. An agent for improving hypophosphatemia comprising, as an active ingredient, a substance capable of inhibiting the binding between parathyroid hormone related protein (PTHrP) and a receptor thereof,

wherein the substance is the humanized antibody of claim 6.

11. A method of inhibiting the binding between PTHrP and a receptor thereof, comprising:

combining the humanized antibody of claim 6 with the PTHrP;

allowing said humanized antibody to bind to PTHrP; and

inhibiting the binding of PTHrP to a PTHrP receptor.

2. An isolated polypeptide comprising an L chain V region of a humanized antibody comprising an amino acid sequence chosen from SEQ ID NOs:

52-55.

3. An isolated polypeptide comprising an H chain V region of a humanized antibody comprising an amino acid sequence as shown in SEQ ID NO:

56.

5. An isolated H chain of a humanized antibody which binds to a human parathyroid hormone related protein, comprising a polypeptide comprising an H chain C region of a human antibody and a polypeptide comprising an H chain V region according to claim 3.