Title:
PROPROTEINS AND METHODS OF USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2010/096838
Kind Code:
A3
Abstract:
The present disclosure provides for proprotein and activatable proprotein compositions. A proprotein contains a functional protein (i.e. a full length protein or functional fragment thereof) which is coupled to a peptide mask that inhibits the binding of the functional protein to its target or binding partner. An activatable proprotein contains a functional protein coupled to a peptide mask, and further coupled to an activatable linker, wherein in an non-activated state, the peptide mask inhibits binding of the functional protein to its target or binding partner and in an activated state the peptide mask does not inhibit binding of the functional protein to its target or binding partner. Proproteins can provide for reduced toxicity and adverse side effects that could otherwise result from binding of a functional protein at non-treatment sites if it were not inhibited from binding its binding partner. Proproteins can further provide improved biodistribution characteristics. Proproteins containing a peptide mask can display a longer in vivo or serum half-life than the corresponding functional protein not containing a peptide mask. The disclosure further provides methods of screening for, making, and using these proproteins.
Inventors:
STAGLIANO NANCY E (US)
WEST JAMES W (US)
KAMATH KATHRYN (US)
BESSETTE PAUL H (US)
SAGERT JASON (US)
WEST JAMES W (US)
KAMATH KATHRYN (US)
BESSETTE PAUL H (US)
SAGERT JASON (US)
Application Number:
PCT/US2010/025121
Publication Date:
April 03, 2014
Filing Date:
February 23, 2010
Export Citation:
Assignee:
CYTOMX THERAPEUTICS INC
STAGLIANO NANCY E (US)
WEST JAMES W (US)
KAMATH KATHRYN (US)
BESSETTE PAUL H (US)
SAGERT JASON (US)
STAGLIANO NANCY E (US)
WEST JAMES W (US)
KAMATH KATHRYN (US)
BESSETTE PAUL H (US)
SAGERT JASON (US)
International Classes:
A01N37/18; A61K38/10
Domestic Patent References:
| WO2000023472A2 | 2000-04-27 | |||
| WO2007099348A2 | 2007-09-07 | |||
| WO2009025846A2 | 2009-02-26 |
Foreign References:
| US7098002B1 | 2006-08-29 | |||
| US20090023602A1 | 2009-01-22 | |||
| US20060078901A1 | 2006-04-13 | |||
| US20050196754A1 | 2005-09-08 | |||
| US20050208558A1 | 2005-09-22 | |||
| US20040213797A1 | 2004-10-28 | |||
| US20070061916A1 | 2007-03-15 | |||
| US20070083334A1 | 2007-04-12 |
Other References:
GUAY ET AL.: "Potency and selectivity of inhibition of cathepsin K, L and S by their respective propeptides.", EUR J BIOCHEM, vol. 267, no. 20, October 2000 (2000-10-01), pages 6311 - 6318, XP055136019
FUNAHASHI ET AL.: "A notch1 ectodomain construct inhibits endothelial notch signaling, tumor growth, and angiogenesis.", CANCER RES, vol. 68, no. 12, 15 June 2008 (2008-06-15), pages 4727 - 4735, XP055136020
BARTENSCHLAGER ET AL.: "Substrate Determinants for Cleavage in cis and in trans by the Hepatitis C Virus NS3 Proteinase.", J VIROLOGY, vol. 69, no. 1, January 1995 (1995-01-01), pages 198 - 205, XP055136021
TAKAGI ET AL.: "A new approach for alteration of protease functions: pro-sequence engineering.", APPL MICROBIOL BIOTECHNOL, vol. 63, no. 1, November 2003 (2003-11-01), pages 1 - 9, XP055136024
SIDHU ET AL.: "Exploring Protein - Protein Interactions with Phage Display.", CHEMBIOCHEM, vol. 4, no. 1, 3 January 2003 (2003-01-03), pages 14 - 25, XP002338908
CHANG ET AL.: "Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model.", BMC CANCER, vol. 87, no. 7, 23 May 2007 (2007-05-23), pages 1 - 6, XP021029154, Retrieved from the Internet [retrieved on 20100720]
CHO ET AL.: "N-terminal Processing Is Essential for Release of Epithin, a Mouse Type Il Membrane Serine Protease.", JOUR BIOL CHEM, vol. 276, no. 48, 30 November 2001 (2001-11-30), pages 44581 - 44589, XP008100687
FUNAHASHI ET AL.: "A notch1 ectodomain construct inhibits endothelial notch signaling, tumor growth, and angiogenesis.", CANCER RES, vol. 68, no. 12, 15 June 2008 (2008-06-15), pages 4727 - 4735, XP055136020
BARTENSCHLAGER ET AL.: "Substrate Determinants for Cleavage in cis and in trans by the Hepatitis C Virus NS3 Proteinase.", J VIROLOGY, vol. 69, no. 1, January 1995 (1995-01-01), pages 198 - 205, XP055136021
TAKAGI ET AL.: "A new approach for alteration of protease functions: pro-sequence engineering.", APPL MICROBIOL BIOTECHNOL, vol. 63, no. 1, November 2003 (2003-11-01), pages 1 - 9, XP055136024
SIDHU ET AL.: "Exploring Protein - Protein Interactions with Phage Display.", CHEMBIOCHEM, vol. 4, no. 1, 3 January 2003 (2003-01-03), pages 14 - 25, XP002338908
CHANG ET AL.: "Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model.", BMC CANCER, vol. 87, no. 7, 23 May 2007 (2007-05-23), pages 1 - 6, XP021029154, Retrieved from the Internet
CHO ET AL.: "N-terminal Processing Is Essential for Release of Epithin, a Mouse Type Il Membrane Serine Protease.", JOUR BIOL CHEM, vol. 276, no. 48, 30 November 2001 (2001-11-30), pages 44581 - 44589, XP008100687
Attorney, Agent or Firm:
ELRIFI, Ivor et al. (Levin Cohn, Ferris, Glovsky and Popeo PC,One Financial Cente, Boston MA, US)
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