US 6,069,134 A · Methods and compositions comprising DNA damaging agents and p53

Abstract

The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

Claims69

Dependent claims

A method of killing a tumor cell in a tumor of a human cancer patient, the method comprising the steps of:

(a) introducing into said tumor an effective amount of polynucleotides encoding a functionally active p53;
(b) expressing said p53 in said tumor cell, thereby enhancing the sensitivity of said tumor cell expressing said p53 to a first DNA damaging agent, and
(c) contacting said tumor cell with said first DNA damaging agent, thereby killing said tumor cell.

Dependencies are inferred from the claim text.

Facts

Application

08/953,290Filed 17 Oct 1997 · division

Priority

6 Mar 1991

Granted

30 May 2000

Term ends

Not estimatedThe source records don’t support an estimate.

Classification21 codes

C07K 14/82
Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof: translation products from oncogenes
A61K 31/4745
Ortho- or peri-condensed with heterocyclic ring systems: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
A61K 31/513
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/704
Attached to a carbocyclic compound, e.g. phloridzin: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin,…

Family

Serial665,538Parent of this continuation-in-part · filed 6 Mar 1991

Serial960,543Parent of this continuation-in-part · filed 13 Oct 1992

Serial145,826Parent of this continuation-in-part · filed 29 Oct 1993

Serial233,002Parent of this division · filed 25 Apr 1994

US 5,747,469 AParent of this division · filed 5 May 1998

US 6,069,134 AThis patent

From the US filing history. Foreign family members aren’t listed.

Methods and compositions comprising DNA damaging agents and p53

Life of this patent

Methods and compositions comprising DNA damaging agents and p53

Life of this patent

Abstract

Claims69