TARGETED DELIVERY TO LEUKOCYTES USING NON-PROTEIN CARRIERS
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Accused Products
Abstract
Disclosed are delivery agents for selective delivery to leukocytes. The leukocyte-selective delivery agents comprise a targeting moiety that selectively binds LFA-I, a non-protein carrier moiety covalently linked to the targeting moiety and a therapeutic agent associated with the carrier moiety. The non-protein carrier moiety comprises a liposome, a micelle, or a polymeric nanoparticle comprised of PLA or PLGA. The delivery agent may be further selective for activated leukocytes by using a targeting moiety that selectively binds LFA-I in its activated conformation. The targeting moiety may comprise an antibody or functional fragment thereof such as an scFV. Appropriate therapeutic agents include a nucleic acid, a small molecule, a polypeptide, and an antibody or functional fragment thereof. Additional examples of therapeutic agents are a small RNA, an antagomir, an LNA, or an antisense oligonucleotide. One such therapeutic agent is an RNA interference molecule such as siRNA, dsRNA, stRNA, shRNA, miRNA. Specific delivery agents are provided. Methods for in vivo, in vitro and ex vivo leukocyte-selective delivery using the delivery agents are also disclosed.
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Citations
32 Claims
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1. (canceled)
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2. A leukocyte-selective delivery agent comprising,
(a) a targeting moiety that selectively binds LFA-1; -
(b) a non-protein carrier moiety covalently linked to the targeting moiety; and (c) a therapeutic agent associated with the carrier moiety. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A method for in vivo activated leukocyte-selective delivery comprising, administering to a subject an activated leukocyte-selective delivery agent comprising,
(a) a targeting moiety that selectively binds LFA-1 in its activated conformation; -
(b) a non-protein carrier moiety covalently linked to the targeting moiety; and (c) a therapeutic agent associated with the carrier moiety; to contact the delivery agent with activated leukocytes of the subject, to thereby selectively deliver the therapeutic agent to activated leukocytes of the subject. - View Dependent Claims (16, 17)
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18. A method for in vivo leukocyte-selective delivery of a therapeutic agent, comprising administering to a subject a leukocyte-selective delivery agent comprising,
(a) a targeting moiety that selectively binds to LFA-1; -
(b) a non-protein carrier moiety covalently linked to the targeting moiety; and (c) a therapeutic agent associated with the carrier moiety;
to contact the delivery agent with leukocytes of the subject, to thereby selectively deliver the therapeutic agent to leukocytes of the subject. - View Dependent Claims (19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
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30. A method for leukocyte-selective delivery comprising:
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(a) providing a leukocyte-selective delivery agent comprising, (1) a targeting moiety that selectively binds LFA-1; (2) a non-protein carrier moiety covalently linked to the targeting moiety, and (3) a therapeutic agent associated with the carrier moiety; (b) contacting the delivery agent to a population of cells comprising leukocytes, to thereby selectively deliver the therapeutic agent to leukocytes in the population of cells. - View Dependent Claims (31, 32)
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Specification