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Antibody molecules to oncogenic isoforms of fibroblast growth factor receptor-2 and uses thereof

A growth factor receptor and fibroblast technology, applied in the field of antibody molecules of oncogenic isoforms of fibroblast growth factor receptor 2 and its application, can solve the problem that chemotherapy regimen patients show obvious survival benefits

Active Publication Date: 2013-07-10
艾托生物有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, chemotherapy regimens did not demonstrate a clear survival benefit in this patient population

Method used

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  • Antibody molecules to oncogenic isoforms of fibroblast growth factor receptor-2 and uses thereof
  • Antibody molecules to oncogenic isoforms of fibroblast growth factor receptor-2 and uses thereof
  • Antibody molecules to oncogenic isoforms of fibroblast growth factor receptor-2 and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0481] Example 1: Isoform-specific epitopes

Embodiment 11

[0482]Example 1.1: FGFR2: Isomer FGFR2-IIIc (SEQ ID NO: 19)

[0483] Isoforms of fibroblast growth factor receptor 2 (FGFR2) are predominantly expressed in hormone-refractory prostate cancer. Alternative use of exon III produces a different sequence on the Ig-like loop of the extracellular domain, which is important for ligand binding. Isoform IIIb is expressed in normal prostate epithelial cells. Malignant prostate cancer cells transform into the IIIc isoform, which has high binding affinity for growth factors with high transforming activity, such as the FGF8b isoform.

[0484] FGFR2-IIIc uses an alternate exon III that encodes a different sequence than the isoform FGFR2-IIIb. In the hydroxyl-terminal region, half of the Ig-ring III, from amino acids 314 to 353, the FGFR2-IIIc isoform contains sequences that are non-homologous to the IIIb isoform. The isomeric structure of FGFR2 is as figure 1 shown.

[0485] A sequence alignment of the IIIc and IIIb isoforms shows a di...

Embodiment 12

[0489] Example 1.2: FGFR1: isoform FGFR1L (deletion of exons 7 & 8; 105 amino acids; part Ig-II and part Ig-III)

[0490] The isoform structure of fibroblast growth factor receptor 1 (FGFR1) as Figure 7 shown. The amino acid (SEQ ID NO:10) and nucleotide (SEQ ID NO:9) sequence of the epitope located at the junction (junction) is as follows Figure 8 shown.

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Abstract

Antibody molecules that specifically bind to one or more isoforms expressed and / or associated with oncogenic phenotypes in a hyperproliferative cell (e.g., a cancerous or tumor cell) are disclosed. The isoform-binding antibody molecules can be used to treat, prevent and / or diagnose cancerous conditions and / or disorders. Methods of using the isoform-binding molecules to selectively detect oncogenic isoforms, to reduce the activity and / or induce the killing of a hyperproliferative cell expressing an oncogenic isoform in vitro, ex vivo or in vivo are also disclosed. Diagnostic and / or screening methods and kits for evaluating the function or expression of an oncogenic isoform are also disclosed.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 61 / 373,072, filed August 12, 2010, the contents of which are hereby incorporated by reference in their entirety. [0003] sequence listing [0004] This application includes a Sequence Listing submitted in ASCII format via EFS-Web, which is hereby incorporated by reference in its entirety. The above ASCII copy was created on August 12, 2011 and is named A20497WO.txt and is 301,554 bytes in size. [0005] Government funding [0006] The work described herein was performed at least in part using Contract No. [0007] 1R43CA137929-01 funded. Accordingly, the United States Government may have certain rights in this invention. Background technique [0008] Despite numerous advances in medical research, cancer remains a leading cause of death in the United States. Traditional models of clinical care, such as surgical resection, radiotherapy, and ch...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/00A61K39/395
CPCC07K16/2863C07K2317/33C07K2317/34C07K2317/622C07K2317/76
Inventor 常小迦乌尔里克·S.·斯施瓦楚拉格凯瑟琳·简·图纳尔
Owner 艾托生物有限公司
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