Human and mouse targeting peptides identified by phage display

a technology of human and mouse, which is applied in the field of molecular medicine and targeted delivery of therapeutic agents, can solve the problems of slow and laborious process of identification of previously unknown receptors and previously uncharacterized ligands, and limited treatment of many disease states

Inactive Publication Date: 2004-09-02
BOARD OF RGT THE UNIV OF TEXAS SYST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therapeutic treatment of many disease states is limited by the systemic toxicity of the therapeutic agents used.
In some cases, previous in vivo methods for phage display screening resulted in relatively high backgrounds of non-specific phage binding.
Identification of previously unknown recep

Method used

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  • Human and mouse targeting peptides identified by phage display
  • Human and mouse targeting peptides identified by phage display
  • Human and mouse targeting peptides identified by phage display

Examples

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Effect test

example 1

Bone Marrow Targeting Peptides

[0180] A non-limiting example of an organ of specific interest for targeting petides is bone marrow. Bone is the preferred site of metastasis in the large majority of patients with prostate cancer (Fidler, 1999). This striking selectivity has been viewed as an example of site-specific interactions that were essential to cancer progression (Rak, 1995; Zetter, 1998). Despite the clinical relevance, little is known about the mechanisms that control prostate cancer spread to bone. In addition, there were no effective strategies for targeting therapeutic agents for the treatment of metastatic prostate cancer (Brodt et. al, 1996).

[0181] A subset of peptides capable of selective homing to bone marrow through the circulation is likely to simulate the behavior of prostate cancer cells during bone metastasis formation. The vascular markers targeted by using phage display might also be utilized by tumor cells to metastasize. This concept has already been proven to...

example 2

Prostate and Prostate Cancer Targeting Peptides

[0192] Another non-limiting organ of particular interest for targeting is the prostate. Prostate is an unusual organ because it continues to growth throughout adult life. As a result, benign prostate hypertrophy (BPH) affects most elderly men to some degree. Even more serious, the prostate is a frequent site of malignant tumors. One out of eleven men will develop prostate cancer during their lifetime. Because serum markers for prostate cancer were available, many of these malignant tumors were currently detected early in the course of the disease. In the absence of reliable ways of predicting which ones will progress clinically, many were aggressively treated with surgery or radiotherapy, often with devastating side-effects such as incontinence and impotence (Lane and Shah, 1999; Mikolajczyk et al., 2000). There is a clear need for improved methods for detection, prognosis, and treatment of human prostate cancer.

[0193] Many interesting ...

example 3

Identification of Mouse Placenta, Adipose, Ovary and Ureter Targeting Peptides

[0209] Identification of Placenta Homing Peptides

[0210] Peptides homing to the mouse placenta were identified by a post-clearing protocol using a phage display library. A first round of biopanning was performed on pregnant mice. Samples of placenta were removed and phage rescued according to the standard protocols described above, with one modification. In the typical bipanning protocol, thousands of phage may be recovered from a single organ, tissue or cell type. Typically, between 200 and 300 individual colonies were selected from plated phage and these were amplified and pooled to form the phage display library for the second or third rounds of biopanning. In this example, all phage rescued from the first round of biopanning were amplified in bulk on solid medium and then pooled to form the phage display library for the second round of biopanning. That is, there was no restriction of the rescued phage f...

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Abstract

The present invention concerns methods and compositions for in vivo and in vitro targeting. A large number of targeting peptides directed towards human organs, tissues or cell types are disclosed. The peptides are of use for targeted delivery of therapeutic agents, including but not limited to gene therapy vectors. A novel class of gene therapy vectors is disclosed. Certain of the disclosed peptides have therapeutic use for inhibiting angiogenesis, inhibiting tumor growth, inducing apoptosis, inhibiting pregnancy or inducing weight loss. Methods of identifying novel targeting peptides in humans, as well as identifying endogenous receptor-ligand pairs are disclosed. Methods of identifying novel infectious agents that are causal for human disease states are also disclosed. A novel mechanism for inducing apoptosis is further disclosed.

Description

[0001] This application claims priority from U.S. Provisional Patent Application No. 60 / 231,266 filed Sep. 8, 2000, and U.S. patent application Ser. No. 09 / 765,101, filed Jan. 17, 2001.[0003] 1. Field of the Invention[0004] The present invention concerns the fields of molecular medicine and targeted delivery of therapeutic agents. More specifically, the present invention relates to compositions and methods for identification and use of peptides that selectively target organs tissues or cell types in vivo or in vitro.[0005] 2. Description of Related Art[0006] Therapeutic treatment of many disease states is limited by the systemic toxicity of the therapeutic agents used. Cancer therapeutic agents in particular exhibit a very low therapeutic index, with rapidly growing normal tissues such as skin and bone marrow affected at concentrations of agent that are not much higher than the concentrations used to kill tumor cells. Treatment of cancer and other organ, tissue or cell type confined...

Claims

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Application Information

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IPC IPC(8): A61K38/00C07K7/06C07K7/08C07K14/00C12N15/10C40B40/02
CPCA61K38/00C07K7/06C07K7/08C40B40/02C12N15/1037C12N2810/40C07K14/001A61P1/00A61P11/00A61P15/00A61P19/02A61P27/02A61P29/00A61P3/04A61P31/00A61P31/04A61P31/12A61P35/00A61P37/04A61P7/12A61P9/00A61P9/10A61P3/10
Inventor ARAP, WADIHPASQUALINI, RENATA
Owner BOARD OF RGT THE UNIV OF TEXAS SYST
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