Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Pharmaceutically acceptable FN3 polypeptides for human treatments

a technology of fn3 polypeptides and human treatment, applied in the field of protein scaffolds, can solve the problems of somewhat limited utility of framework, and achieve the effects of optimal folding, stability, and solubility

Inactive Publication Date: 2006-11-02
BRISTOL MYERS SQUIBB CO
View PDF22 Cites 108 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a new family of proteins that can be designed to bind to any compound of interest. These proteins are derived from a scaffold called fibronectin type III (Fn3) and are designed to have optimal folding, stability, and solubility under conditions that normally lead to the loss of structure and function in antibodies. These proteins can be used as scaffolds to create new molecules that can bind to any target compound with high affinity. The invention features randomized or mutated scaffold proteins, non-antibody proteins, and fusion proteins with Fn3 domains. The Fn3 domain-containing proteins have been found to bind to compounds with high affinity and can be derived from a variety of reference proteins.

Problems solved by technology

These two loops have been randomized and products selected for antigen binding, but thus far the framework appears to have somewhat limited utility due to solubility problems.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Pharmaceutically acceptable FN3 polypeptides for human treatments
  • Pharmaceutically acceptable FN3 polypeptides for human treatments
  • Pharmaceutically acceptable FN3 polypeptides for human treatments

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0080] The novel antibody mimics described herein have been designed to be superior both to antibody-derived fragments and to non-antibody frameworks, for example, those frameworks cited above.

[0081] The major advantage of these antibody mimics over antibody fragments is structural. These antibody mimics are derived from whole, stable, and soluble structural scaffolds. For example, the Fn3 scaffold is found in the human body. Consequently, they exhibit better folding and thermostability properties than antibody fragments, whose creation involves the removal of parts of the antibody native fold, often exposing amino acid residues that, in an intact antibody, would be buried in a hydrophobic environment, such as an interface between variable and constant domains. Exposure of such hydrophobic residues to solvent increases the likelihood of aggregation of the antibody fragments.

[0082] In addition, the scaffolds described herein have no disulfide bonds, which have been reported to reta...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
melting temperatureaaaaaaaaaa
melting temperatureaaaaaaaaaa
pHaaaaaaaaaa
Login to View More

Abstract

Disclosed herein are proteins that include an immunoglobulin fold and that can be used as scaffolds. Also disclosed herein are nucleic acids encoding such proteins and the use of such proteins in diagnostic methods and in methods for evolving novel compound-binding species and their ligands.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This continuation application claims the benefit of continuation-in-part application, U.S. Ser. No. 09 / 688,566, filed Oct. 16, 2000, continuation-in-part application, U.S. Ser. No. 09 / 515,260, filed Feb. 29, 2000, utility application, U.S. Ser. No. 09 / 456,693, filed Dec. 9, 1999, and provisional application U.S. Ser. No. 60 / 111,737, filed Dec. 10, 1998, (now abandoned).BACKGROUND OF THE INVENTION [0002] This invention relates to protein scaffolds useful, for example, for the generation of products having novel binding characteristics. [0003] Proteins having relatively defined three-dimensional structures, commonly referred to as protein scaffolds, may be used as reagents for the design of engineered products. These scaffolds typically contain one or more regions which are amenable to specific or random sequence variation, and such sequence randomization is often carried out to produce libraries of proteins from which desired products ma...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395C07K16/46C12N1/21C12P21/04C07K14/47C07K14/525C07K14/78C07K16/00C07K16/24C12N15/10C12Q1/00C40B40/02
CPCC07K14/47C07K14/525C07K14/78C07K16/00C07K16/241C40B40/02C07K2318/20C07K2319/00C07K2319/30C12N15/1037C12Q1/00C07K2317/22
Inventor LIPOVSEK, DASAWAGNER, RICHARD W.KUIMELIS, ROBERT G.
Owner BRISTOL MYERS SQUIBB CO
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products