Binding ligand linked drug delivery conjugates of tubulysins

a technology of tubulysin and binding ligand, which is applied in the direction of drug composition, peptide/protein ingredients, peptides, etc., can solve the problems of complex approaches and adverse side effects of the currently available chemotherapeutic agents and radiation therapy regimens

Inactive Publication Date: 2014-03-06
ENDOCTYE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, many of the currently available chemotherapeutic agents and radiation therapy regimens have adverse side effects because they work not only to destroy pathogenic cells, but they also affect normal host cells, such as cells of the hematopoietic system.
However, these approaches have been complicated by the difficulties in defining tumor-specific antigens.

Method used

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  • Binding ligand linked drug delivery conjugates of tubulysins
  • Binding ligand linked drug delivery conjugates of tubulysins
  • Binding ligand linked drug delivery conjugates of tubulysins

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[0224]The compounds described herein may be prepared using the process and syntheses described herein, as well as using general organic synthetic methods. In particular, methods for preparing the compounds are described in U.S. patent application publication 2005 / 0002942, the disclosure of which is incorporated herein by reference.

[0225]General formation of folate-peptides. The folate-containing peptidyl fragment Pte-Glu-(AA)n-NH(CHR2)CO2H (3) is prepared by a polymer-supported sequential approach using standard methods, such as the Fmoc-strategy on an acid-sensitive Fmoc-AA-Wang resin (1), as shown in the following Scheme:

[0226]In this illustrative embodiment of the processes described herein, R1 is Fmoc, R2 is the desired appropriately-protected amino acid side chain, and DIPEA is diisopropylethylamine. Standard coupling procedures, such as PyBOP and others described herein or known in the art are used, where the coupling agent is illustratively applied as the act...

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Abstract

Described herein are compounds, pharmaceutical compositions and methods for treating pathogenic cell populations. The compounds described herein include conjugates of tubulysins and vitamin receptor binding ligands. The conjugates also include a releasable bivalent linker.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority under 35 U.S.C. §119(e) of U.S. provisional patent application Ser. No. 60 / 911,551 filed Apr. 13, 2007, and U.S. provisional patent application Ser. No. 60 / 894,901 filed 14 Mar. 2007, the disclosures of which are incorporated herein by reference in their entirety.TECHNICAL FIELD[0002]The present invention relates to compositions and methods for use in targeted drug delivery. More particularly, the invention is directed to cell-surface receptor binding drug delivery conjugates for use in treating disease states caused by pathogenic cell populations and to methods and pharmaceutical compositions that use and include such conjugates.BACKGROUND[0003]The mammalian immune system provides a means for the recognition and elimination of tumor cells, other pathogenic cells, and invading foreign pathogens. While the immune system normally provides a strong line of defense, there are many instances wher...

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K7/06
CPCA61K47/48107A61K47/48338C07K5/021A61K51/0497C07K7/06A61K47/481A61K47/48246C07K5/06078A61K47/65A61K47/55A61K47/551A61K47/64A61P35/00A61P43/00A61K47/6811
Inventor VLAHOV, IONTCHO R.LEAMON, CHRISTOPHER P.WANG, KEVIN YU
Owner ENDOCTYE INC
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