Modified transferrin-antibody fusion proteins

A technology of fusion protein and transferrin, which is applied in the direction of fusion polypeptide, peptide/protein component, antibody mimic/scaffold, etc., which can solve the problems of limited access to the target site, difficulty in preparation, expensive monoclonal antibody, etc.

Inactive Publication Date: 2005-11-09
BIOREXIS PHARMA CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, monoclonal antibodies are expensive and difficult to produce
In addition, monoclonal antibodies are relatively large, limiting their access to the target site

Method used

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  • Modified transferrin-antibody fusion proteins
  • Modified transferrin-antibody fusion proteins
  • Modified transferrin-antibody fusion proteins

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0420] Transbodies comprising transferrin molecules and single chain antibodies can be prepared. A specific example of an SCA that can be fused to transferrin is anti-TNF (Tumor Necrosis Factor). Anti-TNF can be used to treat various inflammatory and autoimmune diseases such as rheumatoid arthritis. TNF-SCA can be fused to the N- or C-terminus of the modified transferrin in such a way that the N-terminus of the encoded TNF-SCA is directly linked to the C-terminal amino acid of transferrin, or the TNF-SCA The C-terminus of the protein is directly linked to the N-terminal amino acid of transferrin. Alternatively, a peptide linker can be inserted to provide greater separation between transferrin and TNF-SCA, allowing more steric flexibility for the two fusion proteins. Multiple TNF-SCA examples are shown in Figures 4A-4B.

[0421] Modified Tf (mTf) and TNF are prepared by fusing one or more copies of the nucleotide sequence encoding SCA to the Tf nucleotide sequence to prepare...

Embodiment 2

[0527] Preparation of trans-bodies containing transferrin and CDRs. These transsomes consist of relatively short peptide chains. Antibodies typically have 3 CDRs in their heavy chain and 3 CDRs in their light chain. One or more CDRs of antibodies capable of interacting with the antigen are fused to the modified transferrin, so that the transferrin molecule has antigen-binding activity. CDRs can be fused to the N-terminus, C-terminus, N-terminus and C-terminus, or genetically engineered into the internal scaffold of transferrin. Examples of CDR sequences from anti-TNF antibodies are shown in TNF-SCA Figures 4A-4B. The cDNA corresponding to one or more CDRs can be fused to the modified transferrin, so that the transferrin has TNF binding activity.

[0528] Insertion of CDR(s)

[0529] N 1

N 2

Asp33

Ser105

Asn55

Glu141

Asn75

Asp166

Asp90

Gln184

Gly257

Asp197

Lys280

Lys217

His289

...

Embodiment 3

[0627] The transbodies in Examples 1 and 2 can also be further modified to include antigenic or immunomodulatory peptides. Desired peptides can be inserted into the transferrin portion of the trans-body. In this way, the modified transsome is able not only to bind its antigen but also to induce an immune response in the host.

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Abstract

Fusion proteins of transferrin and other therapeutic moieties with increased serum half-life or serum stability are disclosed. Preferred fusion proteins include those modified so that the transferrin moiety exhibits no or reduced glycosylation, binding to iron and / or binding to the transferrin receptor.

Description

[0001] related application [0002] This application claims priority to and the benefit of earlier U.S. Provisional Patent Application 60 / 406,977, filed August 30, 2002, and U.S. Patent Application 10 / 384,060, filed March 10, 2003, both of which are hereby incorporated in their entirety Reference. technical field [0003] The present invention relates to a therapeutic protein or peptide fused or inserted into a transferrin molecule with improved serum stability or in vivo circulating half-life, the transferrin molecule modified to reduce or inhibit glycosylation, and / or reduce or Inhibits iron binding and / or transferrin receptor binding. In particular, the invention includes single chain antibodies fused or inserted into transferrin molecules or modified transferrin molecules. Background technique [0004] Therapeutic proteins or peptides in natural state or recombinantly produced are usually unstable molecules with a short period of serum stability or a short circulating ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H21/04C12N15/63C12N15/65C12N15/86A01K67/00C07K16/00A61K39/395A61K38/00A61K47/48C07K7/06C07K7/08C07K14/705C07K14/79
CPCC07K2319/00C07K7/06C07K14/47C12N2740/16122A01K2217/05C07K14/005A61K38/40C07K14/565C07K2319/31C07K2319/035A61K47/483C07K2319/40C07K7/08C07K14/70582C07K14/79A61K47/644A61P15/00A61P15/08A61P19/02A61P25/00A61P29/00A61P31/00A61P31/04A61P31/12A61P31/14A61P31/18A61P31/20A61P33/00A61P35/00A61P3/08A61P37/02A61P37/06A61P43/00A61P7/06A61P3/10
Inventor 霍马扬·萨德吉克里斯托弗·P·普里奥尔安德鲁·特纳
Owner BIOREXIS PHARMA CORP
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