Bone morphogenetic protein-2 in the treatment and diagnosis of cancer

• US 7,473,561 B2
• Filed: 05/17/2006
• Issued: 01/06/2009
• Est. Priority Date: 01/12/2001
• Status: Expired due to Fees

• Current Assignee: Rutgers University
• Original Assignee: University of Medicine and Dentistry of New Jersey (State of New Jersey)
• Inventors: Langenfeld, John
• Primary Examiner(s): Rawlings; Stephen L
• Application Number:
  US11/435,852
• Publication Number:
  US 20060198844A1
• Time in Patent Office: 965 Days
• Field of Search: 436/501, 435/4, 530/350
• US Class Current: 436/501
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: G01N 2333/51 Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: G01N 2333/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 2500/10 involving cells
• CPC Class Codes: G01N 33/57423 of lung
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

The present invention pertains to the use of BMP-2, which is overexpressed in most common cancers, as 1) a target for cancer treatment therapies and 2) a means to diagnose cancer. The therapeutic component of this invention involves administering to a patient a composition that inhibits bone morphogenetic-2 activity. Such inhibition may be accomplished by ligands or antibodies that bind to BMP-2 or BMP-2 receptors. It may also be achieved by preventing the processing of pro-BMP-2, or blocking transcription or replication of BMP-2 DNA or translation of BMP-2 mRNA. The diagnostic component of the invention involves measuring the BMP-2 level in biological samples from both a patient and a subject and comparing those levels. Elevated levels of BMP-2 in the patient compared to the non-cancerous subject indicate cancer.

Claims

1. A method for identifying a candidate agent for use in reducing vascularization in non-small cell lung tumors comprising:

(a) contacting bone morphogenetic protein-2 (BMP-2) and BMP-2 receptor IB in the presence of a test agent under conditions suitable to permit the formation of a BMP-2/BMP-2 receptor complex, wherein said BMP-2 comprises the amino acid sequence of amino acids 283-396 of SEQ ID NO;

2 and wherein said BMP-2 receptor IB comprises the amino acid sequence of amino acids 14-502 of SEQ ID NO;

14;

(b) determining the amount of the BMP-2/BMP-2 receptor complex formed in the presence of said test agent; and

(c) determining that said test agent is a candidate agent for use in reducing vascularization in non-small cell lung tumors if the amount of the BMP-2/BMP-2 receptor complex formed in the presence of said test agent is lower than the amount of the BMP-2/BMP-2 receptor complex formed in the absence of said test agent,

thereby identifying a candidate agent for use in reducing vascularization in non-small cell lung tumors.