Detection and visualization of neoplastic tissues and other tissues
First Claim
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1. A method for in vivo labeling of selected tissues, comprising:
- contacting the tissue with a conjugate comprising a first component of a bioluminescence generating system, wherein the first component is a luciferin or luciferase; and
then contacting the tissue with other components of the bioluminescence generating system, wherein;
contacting is effected in vivo.
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Abstract
Kits containing the diagnostic systems and diagnostic systems that rely on bioluminescence for visualizing tissues in situ are provided. The systems include compositions containing conjugates that include a tissue specific, particularly a tumor-specific, targeting agent linked to a targeted agent, a luciferase or luciferin. The systems also include a second composition that contains the remaining components of a bioluminescence generating reaction. Administration of the compositions results production of light by targeted tissues that permits the detection and localization of neoplastic tissue for surgical removal.
282 Citations
27 Claims
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1. A method for in vivo labeling of selected tissues, comprising:
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contacting the tissue with a conjugate comprising a first component of a bioluminescence generating system, wherein the first component is a luciferin or luciferase; and
then contacting the tissue with other components of the bioluminescence generating system, wherein;
contacting is effected in vivo. - View Dependent Claims (2, 3, 15, 16)
fireflies, Mnemiopsis, Beroe ovata, Aequorea, Obelia, Pelagia, Renilla, Pholas Aristostomias, Pachystomias, Poricthys, Cypridina, Aristostomias, such Pachystomias, Malacosteus, Gonadostomias, Gaussia, Watensia, Halisturia, Vampire squid, Glyphus, Mycotophids, Vinciguerria, Howella, Florenciella, Chaudiodus, Melanocostus, Sea Pens, Chiroteuthis, Eucleoteuthis, Onychoteuthis, Watasenia, cuttlefish, Sepiolina, Oplophorus, Acanthophyra, Sergestes, Gnathophausia, Argyropelecus, Yarella, Diaphus, Gonadostomias and Neoscopelus.
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4. A method for in vivo or in situ labeling or visualizing selected tissues, comprising:
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(a) administering a first composition comprising, in a pharmaceutically acceptable vehicle, a conjugate that comprises a targeted agent that is a component of the bioluminescence generating system, and a targeting agent, wherein the conjugate binds to a cell surface receptor, the targeted agent is a luciferase or luciferin, the targeting agent specifically binds to a cell surface protein; and
(b) administering a second composition, comprising, in a pharmaceutically acceptable vehicle, another component of the bioluminescence generating system, wherein;
the bioluminescence generating system comprises a luciferase and a luciferin;
the first composition and second composition are administered simultaneously, or successively. - View Dependent Claims (5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
(targeting agent)n, (L)q and (targeted agent)m, wherein;
L is a linker;
the targeting agent is a protein or peptide that specifically binds to a cell surface protein;
at least one targeting agent is linked at any residue polypeptide via (L)q to at least one targeted agent;
m and n, which are selected independently, are at least 1;
q is 0 or more as long as the resulting conjugate binds to a cell surface protein on the targeted cells.
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6. The method of claim 4, wherein m and n, which are selected independently, are 1-6.
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7. The method of claim 6, wherein q is 1, n is 1 and m is 1.
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8. The method of claim 5, wherein L is selected from the group consisting of protease substrates, linkers that increase the flexibility of the conjugate, linkers that increase the solubility of the conjugate, linkers that increase the serum stability of the conjugate, photocleavable linkers and acid cleavable linkers.
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9. The method of claim 5, wherein the targeting agent is a monoclonal antibody or a growth factor.
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10. The method of claim 5, wherein the targeting agent is a tumor specific antibody.
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11. The method of claim 5, wherein the conjugate is a chimeric protein produced by fusing a luciferase to a targeting agent.
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12. The method of claim 5, wherein the conjugate is a non-covalent complex containing a targeting agent and a luciferin or luciferase.
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13. The method of claim 4, wherein the bioluminescence generating system is selected from the group consisting of those isolated from the ctenophores, coelenterates, mollusca, fish, ostracods, insects, bacteria, a crustacea, annelids, and earthworms.
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14. The method of claim 4, wherein the bioluminescence generating system is selected from those isolated from:
fireflies, Mnemiopsis, Beroe ovata, Aequorea, Obelia, Pelagia, Renilla, Pholas Aristostomias, Pachystomias, Poricthys, Cypridina, Aristostomias, such Pachystomias, Malacosteus, Gonadostomias, Gaussia, Watensia, Halisturia, Vampire squid, Glyphus, Mycotophids, Vinciguerria, Howella, Florenciella, Chaudiodus, Melanocostus, Sea Pens, Chiroteuthis, Eucleoteuthis, Onychoteuthis, Watasenia, cuttlefish, Sepiolina, Oplophorus, Acanthophyra, Sergestes, Gnathophausia, Argyropelecus, Yarella, Diaphus, Gonadostomias and Neoscopelus.
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17. The method of claim 4, wherein the first composition is administered systemically.
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18. The method of claim 4, wherein the first and second composition are administered systemically.
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19. The method of claim 4, wherein the first composition is administered systemically prior to a surgical procedure, and, the second composition is applied topically during the surgical procedure.
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20. The method of claim 4, wherein the first composition is administered systemically prior to a surgical procedure, and, the second composition is administered locally the surgical procedure.
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21. The method of claim 4, wherein the targeting agent is a tumor specific antibody.
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22. The method of claim 21, wherein the antibody is selected from the group consisting of FO23C5, A10, MN14 F(ab)2, MAb J28, MAb PA8-15, MAb C 50, MAb 19-9, MAb C 242, MAb AR-3, MAb DU-PAN-2, MAb Ypan-1, MAb Span-1, MAb BW494, MAb MUSE 11, MAb 17-1A, OC125, DF3, GA733MoAb, YH206MoAb and A78-G/A7.
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23. The method of claim 21, wherein detecting method is non-invasive;
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both compositions are administered systemically; and
resulting light can be detected by scanning or viewing the surface of the body.
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24. The method of claim 4, wherein one or both compositions are administered by topical, enteric, local, parenteral, intracystal, intracutaneous, intravitreal, subcutaneous, intramuscular, or intravenous administration.
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25. The method of claim 4, further comprising detecting the emitted light.
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26. The method of claim 21, wherein the tumor is selected from the group consisting of melanoma, lymphoma, osteosarcoma, glioma, leukemia, teratocarcinoma, adenocarcinoma, colorectal carcinoma, primary hepatoma, lung carcinoma, mucinous cystadenocarcinoma, hepatocellular carcinoma, medulloblastoma, pancarcinoma, squamous tumors, neuroblastoma, gastrointestinal carcinoma, medullary thyroid carcinoma, breast tumors, brain tumors, ovarian tumors, cervical tumors, prostate tumors, bladder tumors and meningioma.
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27. The method of claim 21, wherein the antibody is humanized.
Specification