Composition and methods for affecting metallocorrinoid uptake

Inactive Publication Date: 2007-05-10
BAUER JOSEPH A +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013] The multiple components of Cb1 uptake, enzymes, co-factors, and transport systems present several points of attack for the therapeutic delivery of cobalamins. As is described herein, the interrelationship of TCII-R and cytokines make this an attractive target for the therapeutic delivery of biologically active metallocorrinoids. Cytokines, in particular interferon β, are shown to enhance the uptake or activity of biologically active metallocorrinoids, including vitamin B12 analogs, homologs, and derivatives.
[0025] Yet another embodiment of the present invention is a method of enhancing bio-availability of a metallocorrinoid, comprising the step of administering interferon-β alone or in combination with a metallocorrinoid.
[0027] Yet another embodiment of the present invention is a method of treating cancer comprised of administering a cytokine (e.g. interferon-β) to enhance the uptake or increase the availability of cobalamin analogs, homologs, or derivatives. This can be done either alone or in combination with the cobalamin analog, homolog, or derivative.

Problems solved by technology

There may be irreversible damage to the nervous system with specific demyelination of the spinal cord.

Method used

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  • Composition and methods for affecting metallocorrinoid uptake
  • Composition and methods for affecting metallocorrinoid uptake
  • Composition and methods for affecting metallocorrinoid uptake

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Embodiment Construction

[0039] While not wishing to be bound by theory, it appears that the uptake of metallocorrinoids such as vitamin B12, NO-Cb1 or other vitamin B12-based compounds, is dependent upon the TCII receptor, specific for vitamin B12. Because the TCII-R plays a central role in determining metallocorrinoid activity, the relationship between TCII-R and cytokines (e.g. interferons (“IFNs”)) was evaluated. IFNs upregulate the expression of cell surface markers HLA-I, HLA-II, β2 microglobulin, and tumor associated antigens such as CEA and CA 125.

[0040] The present invention provides for an increase in receptor or receptor activity responsible for the uptake of vitamin B12 derived compounds. The administration of cytokines, particularly interferons such as IFN-β, appears to enhance the activity of TCII-R. Administering these cytokines prior to or concurrently with vitamin B12-based compounds increases the delivery of the vitamin B12-based compounds and like metallocorrinoids.

[0041] Increased acti...

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Abstract

The present invention is directed to compositions and methods for affecting metallocorrinoid uptake. The compositions and methods of the present invention are particularly useful in enhancing the uptake or availability of biologically active metallocorrinoids (e.g. cobalamin and its analogs). The present invention is particularly useful in the treatment or prevention of conditions that result from low expression or activity of proteins involved in the processing of metallocorrinoids, as well as in conditions which would benefit from enhanced uptake or availability of cobalamin or its biologically active analogs of cobalamin (e.g. cobalamin drug conjugates).

Description

RELATED APPLICATION(S) [0001] This application is a continuation of U.S. application Ser. No. 10 / 761,870, filed Jan. 21, 2004, which is a continuation of U.S. application Ser. No. 09 / 864,747, filed on May 24, 2001 (Now U.S. Pat. No. 6,752,986, issued on Jun. 22, 2004). [0002] The entire teachings of the above application(s) are incorporated herein by reference.BACKGROUND OF THE INVENTION [0003] Metallocorrinoids are corrin rings with a metal-atom center, such as Co, Fe, Ni, or Mn. A corrin ring is four reduced pyrrole rings linked together. A subclass of naturally occurring metallocorrinoids is known as cobalamin, that is, a cobalt-centered corrin ring. Naturally occurring vitamin B12, for example, is a cobalamin. [0004] Vitamin B12 compounds are known to have many biological functions. They are required by the enzyme methionine synthase, for example, which is involved in the production of DNA. Pregnant women need increased amounts of vitamin B12 which is involved in the production ...

Claims

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Application Information

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IPC IPC(8): A61K38/21A61K31/555A61K31/714
CPCA61K31/555A61K31/714A61K38/215A61K2300/00
InventorBAUER, JOSEPH A.LINDNER, DANIEL J.
OwnerBAUER JOSEPH A