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12/08/05 - USPTO Class 436 |  67 views | #20050272161 | Prev - Next | About this Page  436 rss/xml feed  monitor keywords

Delivery of compounds with rehydrated blood cells

USPTO Application #: 20050272161
Title: Delivery of compounds with rehydrated blood cells
Abstract: Fixed-dried blood cells carrying an active agent are described, along with methods of making the same, methods of using the same, and compositions containing the same. The blood cells may be red blood cells or blood platelets.
(end of abstract)
Agent: Myers Bigel Sibley & Sajovec - Raleigh, NC, US
Inventors: Timothy C. Nichols, Thomas Fischer, Marjorie S. Read
USPTO Applicaton #: 20050272161 - Class: 436063000 (USPTO)

Related Patent Categories: Chemistry: Analytical And Immunological Testing, Biological Cellular Material Tested

Delivery of compounds with rehydrated blood cells description/claims


The Patent Description & Claims data below is from USPTO Patent Application 20050272161, Delivery of compounds with rehydrated blood cells.

Brief Patent Description - Full Patent Description - Patent Application Claims
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RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application Ser. No. 60/533,059, filed Dec. 29, 2003, and U.S. Provisional Patent Application Ser. No. 60/471,005, filed filed May 16, 2003, the disclosures of which are incorporated by reference herein in their entirety.

FIELD OF THE INVENTION

[0003] The present invention concerns methods and compositions for delivering active agents to a subject in need thereof and more particularly to fixed-dried blood cells that carry an active agent and that are useful to deliver active agents to a site of interest.

BACKGROUND OF THE INVENTION

[0004] Platelets have been recognized for decades as potential tools for carrying therapeutics to sites of vascular injury. However, the practical utility of platelets as therapeutic delivery vehicles has been limited because platelets must be freshly isolated, modified with the therapeutic, and then infused in a short time-span. The utility of cryopreserved platelets and normally liquid-stored for therapeutic delivery is limited by storage lesion and, in the case of frozen platelets, the need to remove cryopreservatives. Hence the practical application of cryopreserved platelets, as well as preserved blood cells in general, has been limited.

SUMMARY OF THE INVENTION

[0005] A first aspect of the present invention is fixed-dried blood platelets, red blood cells (RBCs,) or combinations thereof carrying a heterologous compound, active agent or compound of interest, along with compositions comprising, consisting of or consisting essentially of the same. Such platelets, RBCs or combinations thereof are preferably mammalian blood cells such as human blood platelets and RBCs. The compound or active agent may be associated with the platelets and/or RBCs in any manner, such as coupling or by being contained within the platelets and/or RBCs. The platelets and/or RBCs may be aldehyde-fixed, and in one embodiment the platelets are characterized in that they adhere to thrombogenic surfaces; undergo shape change upon adhering to a thrombogenic surface; lead to the formation of a hemostatic plug upon adhering to a thrombogenic surface; and release their granular contents. The active agent or compound to be delivered may be an antiviral agent such as a nucleoside analog antiviral agent (for example ribavirin), a blood coagulation protein such as Factor VII, a nucleic acid (e.g., DNA, RNA), a detectable compound such as a detectable protein or peptide, etc.

[0006] A second aspect of the present invention is a pharmaceutical composition comprising, consisting of or consisting essentially of, for example, from 0.01 or 0.1 to 99.9 or 99.99 percent by weight of a pharmaceutically acceptable carrier (e.g., an aqueous or nonaqueous carrier; a solid, liquid or gel carrier, etc.); and, for example, from 0.01 or 0.1 to 99.9 or 99.99 percent by weight of fixed-dried blood cells carrying an active agent as described herein, the fixed-dried blood cells optionally rehydrated in the pharmaceutically acceptable carrier.

[0007] A further aspect of the present invention is a method of making fixed-dried blood cells for delivering a compound of interest or an active agent to a subject in need thereof, comprising: providing fixed blood cells (typically mammalian cells and preferably human cells, particularly RBCs, platelets, and combinations thereof) carrying the active agent; associating the active agent to the fixed blood cells; and drying the fixed blood cells (e.g., by freeze-drying or lyophilization) to produced fixed-dried blood cells carrying the active compound. The method may further comprise the step of rehydrating the fixed-dried blood cells in a pharmaceutically acceptable carrier to provide a pharmaceuticaly acceptable composition comprising rehydrated fixed-dried blood cells carrying the active agent. The associating step may be carried out by any suitable means, such as by coupling the active agent to the cells or introducing the active agent into the cells. The cells may be aldehyde-fixed platelets, and in one embodiment the cells are platelets that are characterized in that, upon reconstitution, they: adhere to thrombogenic surfaces; undergo shape change upon adhering to a thrombogenic surface; lead to the formation of a hemostatic plug upon adhering to a thrombogenic surface; and release their granular contents.

[0008] A further aspect of the present invention is a method of delivering a compound of interest to a thrombogenic surface (e.g., in a subject, or to a tissue in vitro for diagnostic or compound testing purposes), comprising: providing fixed-dried blood cells carrying the compound of interest as described herein; rehydrating the fixed-dried blood cells in an acceptable carrier (e.g., a pharmaceutically or physiologically acceptable carrier) to provide a composition comprising rehydrated fixed-dried blood cells carrying the active agent; and then administering the pharmaceutical composition (e.g., to the subject, to the tissue in vitro) so that an effective amount of the compound of interest is delivered to a thrombogenic surface. The subject is typically a mammalian subject such as a human subject, and the compound of interest may be a diagnostic or therapeutic agent.

[0009] A further aspect of the present invention is a method of delivering a compound of interest to macrophages of the RES in a subject. The subject is typically a mammalian subject such as a human subject, and the compound of interest may be a diagnostic or therapeutic agent.

[0010] A further aspect of the present invention is a method of delivering an active agent to a site of interest (e.g., to a subject or to a tissue in vitro), comprising: providing fixed-dried blood cells carrying the active agent as described herein; rehydrating the fixed-dried blood cells in a pharmaceutically acceptable carrier to provide a pharmaceuticaly acceptable composition comprising rehydrated fixed-dried blood cells carrying the active agent; and then administering the pharmaceutical composition to the site of interest (e.g., to a subject or to a tissue in vitro), so that an effective amount of the active agent is delivered to said site of interst. The effective amount of active agent may be less than 15% (15 percent) of endogenous platelet equivalent. The subject is typically a mammalian subject such as a human subject, and the active agent may be a diagnostic or therapeutic agent. The cells may be aldehyde-fixed cells, and the subject may for example be afflicted with a vascular injury.

[0011] The foregoing and other objects and aspects of the present invention are explained in greater detail below.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012] FIG. 1 shows the proton NMR Spectra of nucleoside copolymers.

[0013] FIG. 2 shows the fluorescent microscopy of polymer-modified RL platelets.

[0014] FIG. 3 shows ristocetin aggregation of control and polymer modified RL platelets.

[0015] FIG. 4 schematically illustrates the preparation of Platelet/AAV.about.Lac Z reporter conjugates.

[0016] FIG. 5 shows flow cytmometric analysis of rFVIIa-FITC bound to RL platelets.

[0017] FIG. 6 shows that rFVIIa binding to RL:platelets is concentration dependent.

[0018] FIG. 7 shows that rFVIIa is active on the surface of RL platelets.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] The present invention is explained in greater detail below. This description is not intended to be a detailed catalog of all the different ways in which the invention may be implemented, or all the features that may be added to the instant invention. For example, features illustrated with respect to one embodiment may be incorporated into other embodiments, and features illustrated with respect to a particular embodiment may be deleted from that embodiment. In addition, numerous variations and additions to the various embodiments suggested herein will be apparent to those skilled in the art in light of the instant disclosure which do not depart from the instant invention. Hence, the following specification is intended to illustrate some particular embodiments of the invention, and not to exhaustively specify all permutations, combinations and variations thereof.

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