Alternative expression of endogenous telomerase

Because of the direct correlation between length of telomeres and life-span of cells, increasing or causing constitutive expression of telomerase should increase proliferative capacity of cells and bypass or delay the normal onset of senescence.   As you might imagine, many mechanisms and pathways can be exploited to affect telomerase activity.  Maybe for this reason, the claims in this group of patent documents aren’t limited to any particular cell or cell type.  For the patent applications, it remains to be seen if such broad claims will be granted.

The only granted patent in this group – US 5,686,306 assigned to University of Texas – is directed to increasing the length of telomeres in normal cells by providing the cells with an oligonucleotide substrate for telomerase.  Due to the typical approach of filing patent applications early in the research process, often before dissecting biological underpinnings, the claims in patents such as this one may be based on little more than preliminary experiments. While some scientific evidence is presented both in the patent application and in a peer-reviewed journal article (Wright et al. 96 A.D.), judging by the few number of journal articles citing the EMBO Journal paper, it does not appear to have resulted in a quantum leap for therapy.

The remaining patent documents in this area are all applications.  Claims in patent applications will almost always be written broader than what ultimately is granted.  For this reason, these applications will be discussed in general terms; the thrust of the disclosure will be presented in broad brush strokes.

US 2006/0052324, assigned to Stanford University, is directed to conditionally increasing transcription of either TERT or a telomerase RNA component (TERC) in a cell, such that the cell is activated to a proliferative state.   An “agent” is used to increase transcription.  Many different types of agents, e.g., small molecules, are disclosed in the text.  The Examples describe experiments performed using a gene construct in which sequences encoding TERT is under control of a tet promoter.  Treatment with doxycycline turns on transcription.  Much of the Example section is devoted to hair follicle stem cells, leading the reader to surmise that it’s claims to this subject matter that will ultimately be granted.

The remaining document in this area – WO 2006/066247, assigned to Exvivo Technologies – regards technology to enhance hTERT expression and increase processivity of telomerase.  The inventors contemplate a variety of methods to enhance hTERT expression, including treating with hypoxic conditions, up-regulate hypoxia inducible factor, treatment with histone deacetylator inhibitors.  Processivity may be increased by modulation of a “gene responsible for repressing hTERT expression or a gene that is associated with telomerase processivity”.  By “processivity” the applicant means that the telomerase is not prevented or inhibited from extending a telomere.  No data are presented.

As an alternative to treating cells in order to increase endogenous telomerase, one invention, disclosed in patent application US 2006/0160732, provides compositions and methods for inhibiting cell senescence.  In particular, the therapeutic agent is a fusion protein or covalently attached protein comprising telomerase and a tumor suppressor protein (e.g., p53, retinoblastoma protein).  A transport agent, such as an arginine-rich peptide, is also present to ensure that the therapeutic agent is taken up by cells.

Patent Data Title and relevant claims Family Data
US 5,686,306

Assignee:

University of Texas

Earliest priority:

13 May 1992

Filed:

10 Nov 1994

Granted:

11 Nov 1997

Expiry date:

7 Jun 2015

Methods and reagents for lengthening telomeres

Claim 1:  A method for increasing the proliferative capacity of normal cells having telomerase activity, which method comprises culturing or cultivating said cells in the presence of an oligonucleotide substrate for telomerase under conditions such that said oligonucleotide substrate enters said cells and acts to lengthen telomeric DNA of said cells and the proliferative capacity of said cells is increased.

See Appendix 2
US 2006/052324

Assignee:

Leland Stanford Junior University

Earliest priority:

05 Aug 2004

Filed:

04 Aug 2005

Methods and compositions for cell activation

A method for activating a cell comprising:

conditionally increasing transcription of a coding sequence of only one of:

(a) a telomerase reverse transcriptase (TERT), or

(b) a telomerase RNA component (TERC);

in said cell in a manner sufficient to activate said cell

WO 06/031313 A2
US 2006/160732

Assignee:

Inventor –

Aronson, G

Earliest priority:

10 Oct 2003

Filed:

08 Oct 2004

Compositions and methods for inhibiting cell senescence and hyperproliferative disorders

Claim 1:  A composition for inhibiting cell senescence comprising a transport agent and a therapeutic agent, wherein the therapeutic agent comprises a first region having telomerase activity and a second region having tumor suppressor activity.

EP 1673099 A1
WO 05/037297 A1

WO 2006/066247

Assignee:

Exvivo Technologies

Earliest priority:

17 Dec 2004

Filed:

19 Dec 2005

Methods and compositions for extending telomere length and cell lifespan

Claim 1:  A method of elongating a telomere of a cell, the method comprising:

enhancing liTERT expression in the cell; and

increasing telomerase processivity.

No family members