Prevention of ES cell differentiation by ciliary neurotrophic factor

• US 5,332,672 A
• Filed: 04/09/1992
• Issued: 07/26/1994
• Est. Priority Date: 12/02/1991
• Status: Expired due to Term

• Current Assignee: Regeneron Pharmaceuticals Incorporated
• Original Assignee: Regeneron Pharmaceuticals Incorporated
• Inventors: Yancopoulos, George D., Conover, Joanne
• Primary Examiner(s): Hill, Jr., Robert J.
• Assistant Examiner(s): Teng, Sally P.
• Application Number:
  US07/865,878
• Time in Patent Office: 838 Days
• Field of Search: 530/350, 435/240.2, 435/69.1, 435/240.1
• US Class Current: 435/377
• 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 47/62 the modifying agent being a protein, peptide or polyamino acid
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: C07K 14/475 Growth factors; Growth regulators
• CPC Class Codes: C07K 14/71 for growth factors; for growth regulators

Abstract

The present invention provides for a stable, biologically active CNTF/receptor complex, and hybrids or routants thereof. The invention is also based in part on the discovery that the CNTF/receptor complex promotes differentiation through a signal transduction pathway on target cells that do not express the CNTF receptor. The invention further provides for a specific CNTFR mutant that promotes signal transduction without binding CNTF. The invention also provides for a CNTF/receptor blocking mutant, a mutant possessing a high binding affinity to CNTF, but possessing no signal transducing function. The present invention also identifies receptor components shared by the IL-6, CNTF, LIF and OSM signal transduction pathways, and the initiation of signal transduction based upon the presence of such components. The present invention additionally provides for therapeutic and diagnostic applications dependant on the ability of the CNTF/receptor complex, hybrid or mutant to elicit a physiological response on the appropriate target cell.

Claims

1. A method of preventing the differentiation of ES cells comprising:

a) obtaining ES cells

b) culturing said ES cells in the presence of at least about 10 ng/ml ciliary neurotrophic factor.