Modulation of apoptosis with bid

• US 6,326,354 B1
• Filed: 08/19/1998
• Issued: 12/04/2001
• Est. Priority Date: 08/19/1998
• Status: Expired due to Term

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Korsmeyer, Stanley J., Gross, Atan
• Primary Examiner(s): Saunders, David
• Assistant Examiner(s): Tung, Mary Beth
• Application Number:
  US09/136,879
• Time in Patent Office: 1,203 Days
• Field of Search: 435/375, 514/12, 514/21, 530/350
• US Class Current: 514/18.9
• 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: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/4747 Apoptosis related proteins
• CPC Class Codes: C12N 9/6475 Interleukin 1-beta convertase-like enzymes (3.4.22.10; 3.4.22.36; 3.4.22.63)

Abstract

A novel p15 BID polypeptide having cell death agonist activity is disclosed. The p15 BID polypeptide is produced by caspase-cleavage of BID in cells undergoing cell death mediated by TNF or FAS receptors. The p15 BID is useful in methods for modulating death of a target cell which comprise treating the cell with p15 BID. Methods for inhibiting cell death are also described which involve treating a target cell with a mutant p15 BID lacking cell death agonist activity.

Claims

1. An isolated and purified BID polypeptide fragment comprising a p15 BID polypeptide which has cell death activity wherein said fragment does not include full-length BID.

2. The isolated and purified BID polypeptide fragment of claim 1, comprising SEQ ID NO:

3, SEQ ID NO;

4, or SEQ ID NO;

5.

3. The isolated and purified polypeptide of claim 1, consisting of SEQ ID NO:

3, SEQ ID NO;

4, or SEQ ID NO;

5.

4. A composition for promoting death of a target cell which comprises the BID polypeptide fragment of claim 1 and a carrier suitable for facilitating delivery of the BID polypeptide fragment into the cell.

5. The composition of claim 4, wherein the BID polypeptide fragment comprises SEQ ID NO:

3, SEQ ID NO;

4, or SEQ ID NO;

5.

6. The composition of claim 4, wherein the BID polypeptide fragment consists of SEQ ID NO:

3, SEQ ID NO;

4, or SEQ ID NO;

5.