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Monoclonal Antibodies Specific for Human Thymidylate Synthase

Description of Invention:
The antibodies described in this invention detect human thymidylate synthase (TS) in small samples of preserved tissues. TS has traditionally been quantitated with biochemical assays, which have limited sensitivity, require a fair amount of fresh or fresh frozen tissue, and cannot distinguish enzyme activity in heterogeneous cell populations in human tissue. The novel TS-directed antibodies have little cross-reactivity and can be used with several different immunoassay techniques. Sensitive quantification of TS in human tissues can be used to diagnose a patient's stage of cancer, to detect certain metabolic diseases, or to monitor a patient's therapy.

Inventors:
PG Johnston (NCI)
CJ Allegra (NCI)
BA Chabner (NCI)
C-M Liang (NCI)

Patent Status:
DHHS Reference No. E-137-1990/0 --
U.S. Patent 6,221,620 issued 24 Apr 2001

Related Technologies:
DHHS Reference No. E-193-1995/0 --
U.S. Patent Application No. 09/152,647 filed 14 Sep 1998 and U.S. Patent Application No. 09/310,459 filed 12 May 1999, "Methods for Determining the Prognosis of Breast Cancer Using Antibodies Specific for Thymidylate Synthase," PG Johnston, C Allegra (NCI)

DHHS Reference No. E-194-1995/0 --
U.S. Patent 5,998,151 issued 07 Dec 1999, "Method for Predicting the Efficacy of a Chemotherapeutic Regimen for Gastric and Gastrointestinal Cancer Using Antibodies Specific for Thymidylate Synthase," PG Johnston, ER Fisher, CJ Allegra (NCI)


Relevant Publication:
  1. PG Johnston, R Mick, W Recant, KA Behan, ME Dolan, MJ Ratain, E Beckmann, RR Weichselbaum, CJ Allegra, EE Vokes; Thymidylate synthase expression and response to neoadjuvant chemotherapy in patients with advanced head and neck cancer; J Natl Cancer Inst 89(4), 308-313 (1997)
  2. BC Pestalozzi, HF Peterson, RD Gelber, A Goldhirsch, BA Gusterson, H Trihia, J Lindtner, H Cortes-Funes, E Simmoncini, MJ Byrne, R Golouh, CM Rudenstam, M Castiglione-Gertsch, CJ Allegra, PG Johnston; Prognostic importance of thymidylate synthase expression in early breast cancer; J Clin Oncol 15(5), 1923-1931 (1997)
  3. BC Pestalozzi, CJ McGinn, TJ Kinsella, JC Drake, MC Glennon, CJ Allegra, PG Johnston; Increased thymidylate synthase protein levels are principally associated with proliferation but not cell cycle phase in asynchronous human cancer cells; Br J Cancer 71(6), 1151-1157 (1995)
  4. PG Johnston, HJ Lenz, CG Leichman, KD Danenberg, CJ Allegra, PV Danenberg, L Leichman; Thymidylate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors; Cancer Res 55(7), 1407-1412 (1995)
  5. PG Johnston, ER Fisher, HE Rockette, B Fisher, N Wolmark, JC Drake, BA Chabner, CJ Allegra; The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer; J Clin Oncol 12(12), 2640-2647 (1994)
  6. PG Johnston, JC Drake, SM Steinberg, CJ Allegra; Quantitation of thymidylate synthase in human tumors using an ultrasensitive enzyme-linked immunoassay; Biochem Pharmacol 45(12), 2483-2486 (1993)



Portfolios:
Cancer

Cancer -Diagnostics-In Vitro-MAb Based
Cancer -Diagnostics-In Vitro-Other
Cancer -Therapeutics-Immunoconjugates-Mab
Cancer -Diagnostics
Cancer -Therapeutics


For Additional Information Please Contact:
David A. Lambertson Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4632
Email: lambertsond@mail.nih.gov
Fax: (301) 402-0220


Web Ref: 109

Updated: 5/99

 

 
 
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