US5667764A
Expired / Lapsed
US
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Compounds, compositions and methods for binding bio-affecting substances to surface membranes of bio-particles
Assignee: Zynaxis Technologies Inc
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Filing: 1992-05-15
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Granted: 1997-09-16
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Expires: 2012-05-15
Abstract
Abstract Compounds are provided having the capability of binding therapeutically active substances to lipid containing bio-compatible particles, such as cells or viruses. These compounds include a bio-affecting moiety, comprising a therapeutically active substance, which is linked via a linking moiety to at least one hydrocarbon substituent selected so that the compounds is sufficiently non-polar to impart lipid binding capability to the compound. Thus, compounds of the invention are useful for site-selective delivery of therapeutic agents, and retention thereof at the selected site. Methods are provided for using various compounds of the invention in treatment of diseases or other pathological conditions. For example, methods are provided for treatment of: (1) post-angioplasty restenosis; (2) rheumatoid arthritis; (3) tumor cell proliferation, particularly tumor cells associated with ovarian cancer; and (4) psoriasis.
Inventors
- 👤 Gregory A. Kopia
- 👤 Paul K. Horan
- 👤 Brian D. Gray
- 👤 David E. Troutner
- 👤 Katharine A. Muirhead
- 👤 Kamleshkumar A. Sheth
- 👤 Chia-En Lin
- 👤 Zhizhou Yu
- 👤 Bruce D. Jensen
- 👤 Sue Ellen Slezak
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-07 13:59
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/04; C07D209/08; A; A61; A61K; A61K41/00; A61K41/0085; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/60; A61K47/69; A61K47/6901; A61K49/00; A61K49/0002; A61K49/001; A61K49/0013; A61K49/0017; A61K49/0019; A61K49/0021; A61K49/0026; A61K49/0032; A61K49/005; A61K49/0052; A61K49/06; A61K49/18; A61K49/1896; A61K51/00; A61K51/02; A61K51/04; A61K51/0497; A61K51/12; A61K51/1258; A61P; A61P31/00; A61P35/00; C07C; C07C229/00; C07C229/02; C07C229/04; C07C229/06; C07C229/10; C07C229/16; C07D219/00; C07D219/04; C07D219/08; C07D263/00; C07D263/52; C07D263/62; C08; C08B; C08B37/00; C08B37/006; C08B37/0063; C08B37/0075; A61K2121/00; A61K2123/00
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
384 words
A compound having the formula: wherein B represents a chemotherapeutic substance; R and R 1 are substituents independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkaryl and aralkyl, the hydrocarbon chains of which having from 1 to about 30 carbon atoms, and being linear or branched, said substituents being unsubstituted or substituted with one or more non-polar functional groups, one of R or R 1 having at least 12 linear carbon atoms, and the sum of the linear carbon atoms in R and R 1 being sufficient to impart a membrane binding stability of at least 30% to said compound; R 2 represents a spacer moiety of the formula: --(R 3 ) p --Q--(R 4 --Q') q --(R 5 --Q"),--(R 6 --Q"') a --(R 7 Q"").sub.τ -- wherein R 3 represents an aliphatic hydrocarbon, R 4 , R 5 , R 6 and R 7 are independently selected from the group consisting of aliphatic, alicyclic or aromatic hydrocarbons, heterocycles, and CH 2 C(CO 2 M)=CH, Q and Q', Q", Q"' and Q"" are independently selected from the group of functional linkages consisting of amide, thiourea, hydrazone, acyl hydrazone, ketal, acetal, orthoester, ester, anhydride, disulfide, urea, carbamate, imine, amine, ether, carbonate, thioether, sulfonamide carbonyl and amidine linkages; Q', Q", Q"', Q"" may additionally independently represent a valence bond; said aliphatic hydrocarbons having from 1 to 12 linear carbon atoms; said aromatic hydrocarbons having from 6 to 12 carbon atoms; n, p, q, r, s, and t each may be either 0 or 1; X and X 1 may be the same or different and represent O, S, C(CH 3 ) 2 or Se; R 8 is independently selected from the group consisting of H, CE 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 and CH(CH 3 ) 2 ; y may be from 0 to 3; Z represents a substituent selected from the group consisting of H, alkyl, OH, --O--alkyl, COOH, CONH 2 , SO 3 H, SO 2 NH 2 , SH, S-alkyl, CONH-alkyl, CON-(alkyl) 2 , NH-acyl, NH-alkyl, N(alkyl) 2 , NO 2 , halogen, Si(alkyl) 3 , O-Si(alkyl) 3 , Sn(alkyl) 3 and --Hg--halogen, the alkyl groups comprising said Z substituent having from 1 to 4 carbon and A represents a pharmaceutically acceptable anion.
Claim 2
Dependent Claim
384 words
A compound having the formula: wherein B represents a chemotherapeutic substance; R and R 1 are substituents independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkaryl and aralkyl, the hydrocarbon chains of which having from 1 to about 30 carbon atoms, and being linear or branched, said substituents being unsubstituted or substituted with one or more non-polar functional groups, one of R or R 1 having at least 12 linear carbon atoms, and the sum of the linear carbon atoms in R and R 1 being sufficient to impart a membrane binding stability of at least 30% to said compound; R 2 represents a spacer moiety of the formula: --(R 3 ) p --Q--(R 4 --Q') q --(R 5 --Q"),--(R 6 --Q"') a --(R 7 Q"").sub.τ -- wherein R 3 represents an aliphatic hydrocarbon, R 4 , R 5 , R 6 and R 7 are independently selected from the group consisting of aliphatic, alicyclic or aromatic hydrocarbons, heterocycles, and CH 2 C(CO 2 M)=CH, Q and Q', Q", Q"' and Q"" are independently selected from the group of functional linkages consisting of amide, thiourea, hydrazone, acyl hydrazone, ketal, acetal, orthoester, ester, anhydride, disulfide, urea, carbamate, imine, amine, ether, carbonate, thioether, sulfonamide carbonyl and amidine linkages; Q', Q", Q"', Q"" may additionally independently represent a valence bond; said aliphatic hydrocarbons having from 1 to 12 linear carbon atoms; said aromatic hydrocarbons having from 6 to 12 carbon atoms; n, p, q, r, s, and t each may be either 0 or 1; X and X 1 may be the same or different and represent O, S, C(CH 3 ) 2 or Se; R 8 is independently selected from the group consisting of H, CE 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 and CH(CH 3 ) 2 ; y may be from 0 to 3; Z represents a substituent selected from the group consisting of H, alkyl, OH, --O--alkyl, COOH, CONH 2 , SO 3 H, SO 2 NH 2 , SH, S-alkyl, CONH-alkyl, CON-(alkyl) 2 , NH-acyl, NH-alkyl, N(alkyl) 2 , NO 2 , halogen, Si(alkyl) 3 , O-Si(alkyl) 3 , Sn(alkyl) 3 and --Hg--halogen, the alkyl groups comprising said Z substituent having from 1 to 4 carbon and A represents a pharmaceutically acceptable anion.
Claim 3
Dependent Claim
27 words
A compound as claimed in claim 1, comprising a radioisotope selected from the group consisting of radioactive hydrogen, carbon, nitrogen, halogen, sulphur, selenium or a combination thereof.
Claim 4
Dependent Claim
27 words
A compound as claimed in claim 1, wherein said chemotherapeutic substance is selected from the group consisting of immunogens, toxins, hormones, enzymes, antigens, antibodies and antibody fragments.
Claim 5
Dependent Claim
11 words
A compound, according to claim 1 of the formula: ##STR18## .
Claim 6
Dependent Claim
11 words
A compound, according to claim 1, of the formula: ##STR19## .
Claim 7
Dependent Claim
11 words
A compound, according to claim 1, of the formula: ##STR20## .
Claim 8
Dependent Claim
15 words
A compound as claimed in claim 1, wherein said chemotherapeutic substance comprises a nucleic acid.
Claim 9
Dependent Claim
15 words
A compound as claimed in claim 1, wherein said chemotherapeutic agent comprises an anitproliferative agent.
Claim 10
Dependent Claim
25 words
A compound as claimed in claim 8, wherein said antiproliferative agent is selected from the group consisting of colchicine, vinca alkaloids, taxol and derivatives thereof.
Claim 11
Dependent Claim
14 words
A compound as claimed in claim 8, wherein said chemotherapeutic substance comprises an anticoagulant.
Claim 12
Dependent Claim
23 words
A compound as claimed in claim 10, wherein said anticoagulant is selected from the group consisting of heparin, heparin fragments and heparin derivatives.
Claim 13
Dependent Claim
21 words
A compound as claimed in claim 10, wherein said anticoagulant is selected from the group consisting of hirudin and hirudin derivatives.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-09-15 | 2001-03-17 | 2001-09-16 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-09-15 | 2005-03-17 | 2005-09-16 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-09-15 | 2009-03-17 | 2009-09-16 | $7700.00 | Window Closed / Lapsed |