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US5169933A
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Covalently-linked complexes and methods for enhanced cytotoxicity and imaging
Assignee: Poniard Pharmaceuticals Inc
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Filing: 1989-08-07
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Granted: 1992-12-08
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Expires: 2009-08-07
Abstract
Abstract Covalently-linked complexes (CLCs) for targeting a defined population of cells, comprising a targeting protein; a cytotoxic agent; and an enhancing moiety, wherein the enhancing moiety is capable of promoting CLC-target cell interaction are disclosed. Methods for using the claimed CLCs to obtain enhanced in vivo cytotoxicity and enhanced in vivo imaging are also described.
Inventors
- 👤 David C. Anderson
- 👤 A. Charles Morgan, Jr.
- 👤 Paul G. Abrams
- 👤 Alan R. Fritzberg
- 👤 Everett J. Nichols
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 10:21
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/415; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/62; A61K51/00; A61K51/02; A61K51/04; A61K51/08; A61K51/10; A61K51/1093; A61K51/1096; C12; C12N; C12N15/00; C12N15/09; C12N15/11; C12N15/62; A61K2123/00; C07K2319/00; C07K2319/01; C07K2319/10; C07K2319/55
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
51 words
A covalently-linked complex (CLC) for targeting a defined population of cells, comprising: a targeting protein; a cytotoxic agent; and an enhancing moiety, wherein the enhancing moiety promotes CLC-target cell interaction and exhibits alpha helical structure at acidic pH and substantially unfolds at physiological pH and exhibits little or no tertiary structure.
Claim 2
Dependent Claim
51 words
A covalently-linked complex (CLC) for targeting a defined population of cells, comprising: a targeting protein; a cytotoxic agent; and an enhancing moiety, wherein the enhancing moiety promotes CLC-target cell interaction and exhibits alpha helical structure at acidic pH and substantially unfolds at physiological pH and exhibits little or no tertiary structure.
Claim 3
Dependent Claim
22 words
The covalently-linked complex of claim 1 wherein the targeting protein is covalently linked to the cytotoxic agent and to the enhancing moiety.
Claim 4
Dependent Claim
22 words
The covalently-linked complex of claim 1 wherein the cytotoxic agent is covalently linked to the targeting protein and to the enhancing moiety.
Claim 5
Dependent Claim
22 words
The covalently-linked complex of claim 1 wherein the enhancing moiety is covalently linked to the targeting protein and to the cytotoxic agent.
Claim 6
Dependent Claim
63 words
The covalently-linked complex of claim 1 wherein the targeting protein is selected from the group consisting of an antibody, an antibody fragment, an antigen-binding portion of an antibody, a biologically active peptide, a hormone, a growth factor, a biological response modifier, an enzyme, biotin, avidin, analogs thereof that retain the capacity to bind to the defined population of cells, and synthetic targeting proteins.
Claim 7
Dependent Claim
36 words
The covalently-linked complex of claim 1 wherein the cytotoxic agent is a radionuclide; a toxin or a fragment or analog thereof; a drug or an analog thereof; a cytotoxic peptide; or a combination of the foregoing.
Claim 8
Dependent Claim
25 words
The covalently-linked complex of claim 6 wherein the radionuclide is selected from the group consisting of gamma-emitters, positron-emitters, Auger electron-emitters, X-rayemitters, fluorescence-emitters, beta-emitters and alpha-emitters.
Claim 9
Dependent Claim
97 words
The covalently-linked complex of claim 6 wherein the radionuclide is selected from the group consisting of 188 Re, 186 Re, 203 Pb, 212 Pb, 212 Bi, 109 Pd, 64 Cu, 67 Cu, 90 Y, 125 I, 131 I, 77 Br, 211 At, 97 Ru, 105 Rh, 198 Au, 199 Ag, 123 I, 130 I, 133 I, 135 I, 47 Sc, 72 As, 72 Se, 88 Y, 100 Pd, 101m Rh, 119 Sb, 128 Ba, 197 Hg, 111 In, 67 Ga, 68 Ga, 75 Br, 76 Br, 99m Tc, 11 C, 13 N, 15 O and 18 F.
Claim 10
Dependent Claim
34 words
The covalently-linked complex of claim 1 wherein the enhancing moiety is a translocating/internalizing moiety, an anchoring peptide, an accessory moiety, an intracellular retention moiety, a combination peptide, a fusion peptide or a combination thereof.
Claim 11
Dependent Claim
78 words
The covalently-linked complex of claim 9 wherein the translocating/internalizing moiety is selected from the group consisting of aa1-aa2-aa3-EAALA(EALA) 4 -EALEALAA-amide, TAT protein 37-62 fragment, CFITKALGISYGRKKRRQRRRPPQGS, growth factor-derived peptides, peptides containing the sequence CMHIESLDSYTC or CMYIEALDKYAC, estrogens, anti-estrogens peptides of apo-lipoprotein A-1 and B, melittin, bombolittin, delta hemolysin, pardaxins, alamethicin, calcitonin, corticotrophin releasing factor, beta endorphin, glucagon, parathyroid hormone, pancreatic polypeptide, signal sequences, hidden hydrophobic domains, anti-clathrin antibody or fragments thereof, pore-forming proteins, and analogs, derivatives and combinations thereof.
Claim 12
Dependent Claim
12 words
The covalently-linked complex of claim 10 wherein aa1 is cysteine or lysine.
Claim 13
Dependent Claim
29 words
The covalently-linked complex of claim 10 wherein aa2 and aa3 are selected from the group consisting of arginine, lysine, neutral amino acids and peptide spacers having 1-40 amino acids.
Claim 14
Dependent Claim
29 words
The covalently-linked complex of claim 9 wherein the enhancing moiety is covalently linked to the targeting protein or the cytotoxic agent through a peptide spacer having 1-40 amino acids.
Claim 15
Dependent Claim
14 words
The covalently-linked complex of claim 13 wherein the peptide spacer is CDNDNDDNDDGGG or CRQRQRRQRRGGG.
Claim 16
Dependent Claim
29 words
The covalently-linked complex of claim 1 wherein the enhancing moiety is covalently linked to the targeting protein or the cytotoxic agent through a peptide spacer having 1-40 amino acids.
References Cited (Backward Citations)
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