Focused libraries of genetic packages

a technology of genetic packages and libraries, applied in the field of genetic package libraries, can solve the problems of not reflecting, not folding properly, and limited sequence diversity produced by these methods

Inactive Publication Date: 2006-11-16
DYAX CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0087] (7) mixtures of vectors and genetic pack...

Problems solved by technology

Typically, the diversity produced by these methods is limited to sequence diversity, i.e., each member of the library differs from the other members of the family by having different amino acids or variegation at a given position in the peptide, polypeptide or protein chain.
Libraries that contain only amino acid sequence diversity are, thus, disadvantaged in that they do not reflect the natural diversity of the peptide, polypeptide or protein that the library is intended to mimic.
For example, with regard to a library comprising antibody regions, many of the peptides, polypeptides, proteins displayed, displayed and expressed, or comprised by the genetic packages of the library may not fold properly or their bindin...

Method used

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Examples

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Embodiment Construction

ily.

[0091] According to this invention, and as more fully described below, libraries of vectors and genetic packages that more closely mirror the natural diversity, both in sequence and in length, of antibody families, or portions thereof are prepared and used.

Human Antibody Heavy Chain Sequence and Length Diversity

[0092] (a) Framework

[0093] The heavy chain (“HC”) Germ-Line Gene (GLG) 3-23 (also known as VP-47) accounts for about 12% of all human Abs and is preferred as the framework in the preferred embodiment of the invention. It should, however, be understood that other well-known frameworks, such as 4-34, 3-30, 3-30.3 and 4-30.1, may also be used without departing from the principles of the focused diversities of this invention.

[0094] In addition, JH4 (YFDYWGQGTLVTUSS) occurs more often than JH3 in native antibodies. Hence, it is preferred for the focused libraries of this invention. However, JH3 (AFDIWGQGTMVTVSS) could as well be used.

[0095] (b) Focused Length Diversity: ...

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Abstract

Focused libraries of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of antibody peptides, polypeptides or proteins and collectively display, display and express, or comprise at least a portion of the focused diversity of the family. The libraries have length and sequence diversities that mimic that found in native human antibodies.

Description

[0001] This application claims the benefit under 35 USC § 120 of U.S. provisional application 60 / 256,380, filed Dec. 18, 2001. The provisional application and the Tables attached to it are specifically incorporated by reference herein.[0002] The present invention relates to focused libraries of genetic packages that each display, display and express, or comprise a member of a diverse family of peptides, polypeptides or proteins and collectively display, display and express, or comprise at least a portion of the focused diversity of the family. The focused diversity of the libraries of this invention comprises both sequence diversity and length diversity. In a preferred embodiment, the focused diversity of the libraries of this invention is biased toward the natural diversity of the selected family. In a more preferred embodiment, the libraries are biased toward the natural diversity of human antibodies and are characterized by variegation in their heavy chain and light chain complem...

Claims

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Application Information

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IPC IPC(8): C40B30/06C40B40/10G01N33/53C12N15/09C07K16/00C12N15/10C12N15/13C40B40/02
CPCC07K16/005C07K2317/565C07K16/00C40B40/02C12N15/1037C40B40/08C40B40/10
Inventor LADNER, ROBERT
Owner DYAX CORP
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