US4835263A — Novel compounds containing an oligonucleotide seq…

Claim 1

Independent Claim 390 words

An oligonucleotide or an oligodeoxynucleotide consisting of a natural or modified chain of nucleotodes of from 1 to 50 nucleotides or deoxynucleotides to which is attached an intercalating agent via a covalent bond at the 3', 5', or 3' and 5' end or at an internucleotide phosphate of said oligonucleotide or oligodeoxynucleotide, having the formula: ##STR81## in which each B, which are identical or different, represents a base of a natural nucleic acid, selected from the group consisting of thymine, adenine, cytosine, guanine or uracil, or 5-bromo-uracil, 8-azido-adenine, and 2, 6-diamino-purine; each X, which are identical or different, represents an oxoanion O - , a thioanion S - , a C 1 to C 7 alkyl group, a C 1 to C 7 alkoxy group, a monosubstituted or disubstituted amino in the form of quaternary ammonium salt, wherein the substituent is a C 1 to C 7 and wherein the amino is linked to the phosphorous by a straight or branched alkyl or alkoxy chain containing 1 to 10 carbon atoms, a C 1 -C 7 thioalkyl group, or a --Y--Z group; each R and R', which are identical or different, [each ] represents a hydrogen atom or a --Y--Z group; at least one of X, R, or R' is a Y--Z group; provided that: when R or R' is a Y--Z group, Y--Z represents ##STR82## when X is a Y--Z group Y--Z represents --alk--Z, or ##STR83## wherein alk is a straight or branched chain alkylene containing 1 to 10 carbon atoms, each E, which are identical or different, represents an oxoanion O - , a thioanion S - , a C 1 to C 7 alkyl group, a C 1 to C 7 alkoxy group, a monosubstituted or disubstituted amino in the form of quaternary ammonium salt, wherein the substituent is a C 1 to C 7 alkyl and wherein the amino is linked to the phosphorous by a straight or branched alkyl or alkoxy chain containing 1 to 10 carbon atoms, a C 1 -C 7 thioalkyl group; each J, which are identical or different, represents a hydrogen atom or a hydroxyl group; each Z, which are identical or different, [represents an intercalating agent selected from the group consisting of acridine, furocoumarin, ##STR84## and derivatives thereof; and n is an integer having a value from 0 to 50.

Claim 2

Dependent Claim 390 words

An oligonucleotide or an oligodeoxynucleotide consisting of a natural or modified chain of nucleotodes of from 1 to 50 nucleotides or deoxynucleotides to which is attached an intercalating agent via a covalent bond at the 3', 5', or 3' and 5' end or at an internucleotide phosphate of said oligonucleotide or oligodeoxynucleotide, having the formula: ##STR81## in which each B, which are identical or different, represents a base of a natural nucleic acid, selected from the group consisting of thymine, adenine, cytosine, guanine or uracil, or 5-bromo-uracil, 8-azido-adenine, and 2, 6-diamino-purine; each X, which are identical or different, represents an oxoanion O - , a thioanion S - , a C 1 to C 7 alkyl group, a C 1 to C 7 alkoxy group, a monosubstituted or disubstituted amino in the form of quaternary ammonium salt, wherein the substituent is a C 1 to C 7 and wherein the amino is linked to the phosphorous by a straight or branched alkyl or alkoxy chain containing 1 to 10 carbon atoms, a C 1 -C 7 thioalkyl group, or a --Y--Z group; each R and R', which are identical or different, [each ] represents a hydrogen atom or a --Y--Z group; at least one of X, R, or R' is a Y--Z group; provided that: when R or R' is a Y--Z group, Y--Z represents ##STR82## when X is a Y--Z group Y--Z represents --alk--Z, or ##STR83## wherein alk is a straight or branched chain alkylene containing 1 to 10 carbon atoms, each E, which are identical or different, represents an oxoanion O - , a thioanion S - , a C 1 to C 7 alkyl group, a C 1 to C 7 alkoxy group, a monosubstituted or disubstituted amino in the form of quaternary ammonium salt, wherein the substituent is a C 1 to C 7 alkyl and wherein the amino is linked to the phosphorous by a straight or branched alkyl or alkoxy chain containing 1 to 10 carbon atoms, a C 1 -C 7 thioalkyl group; each J, which are identical or different, represents a hydrogen atom or a hydroxyl group; each Z, which are identical or different, [represents an intercalating agent selected from the group consisting of acridine, furocoumarin, ##STR84## and derivatives thereof; and n is an integer having a value from 0 to 50.

Claim 3

Dependent Claim 25 words

The oligonucleotide or oligodeoxynucleotide according to claim 1, wherein B is selected from the group consisting of thymine, adenine, cytosine, guanine, uracil, 5-bromo-uracil, or 8-azido-adenine.

Claim 4

Dependent Claim 128 words

An oligonucleotide or an oligodeoxynucleotide according to claim 1, wherein said oligonucleotide or oligodeoxynucleotide comprising a chain of natural or modified nucleotides or dedeoxynucleotides to which an intercalating group is attached via a covalent bond having the formula: (T--).sub.n (Y.sub.1)Z.sub.1 ; Z.sub.2 (Y.sub.2)(--T).sub.n ; Z.sub.2 (Y.sub.2)(--T).sub.n (Y.sub.1) Z.sub. T-- and --T are a thymidine linked through a phosphodiester bond, n is an integer from 1 to 50, Y 1 and Y 2 are selected from a C-- 1 to C-- 7 alkylene or a ##STR85## wherein p and q are whole numbers from 1 to 10, and Z 1 and Z 2 , which are identical or different, each represents an intercalating agent selected from the group consisting of acridine, furocoumarin, ##STR86## and derivatives of said intercalating agents.

Claim 5

Dependent Claim 87 words

An oligonucleotide or an oligodeoxynucleotide comprising a chain of natural or modified nucleotides or deoxynucleotides to which an intercalating group is attached via a covalent bond having the formula: (A--).sub.n (CH.sub.2).sub.n Z; (G--).sub.n (CH.sub.2).sub.n Z; (C--).sub.n (CH.sub.2).sub.n Z, whe A-- is adenosine linked through a phosphodiester bond, C-- is cytidine linked through a phosphodiester bond, G-- is guanosine linked through a phosphodiester bond, n is an integer from 1 to 25, Z represents an intercalating agent selected from acridine, furocoumarin, ##STR87## and derivatives of said intercalating agents.

Claim 6

Dependent Claim 87 words

An oligonucleotide or an oligodeoxynucleotide comprising a chain of natural or modified nucleotides or deoxynucleotides to which an intercalating group is attached via a covalent bond having the formula: (A--).sub.n (CH.sub.2).sub.n Z; (G--).sub.n (CH.sub.2).sub.n Z; (C--).sub.n (CH.sub.2).sub.n Z, whe A-- is adenosine linked through a phosphodiester bond, C-- is cytidine linked through a phosphodiester bond, G-- is guanosine linked through a phosphodiester bond, n is an integer from 1 to 25, Z represents an intercalating agent selected from acridine, furocoumarin, ##STR87## and derivatives of said intercalating agents.

Claim 7

Dependent Claim 115 words

An oligonucleotide or an oligodeoxynucleotide comprising a natural or modified chain of nucleotides or deoxynucleotides to which an intercalating group is attached via a covalent bond having the sequence selected from the group consisting of: d (A--T--A--A--A--T--T--C--A--C--(CH.sub.2).sub.n Z, d (A--A--T--G--G--T--A--A--A--A--T--(CH.sub.2).sub.n Z), d (T--T--C--T--C--C--C--C--C--A--C--C--A--(CH.sub.2).sub.n Z), d (T--T--T--A--A--(CH.sub.2).sub.n Z), d (T--T--T--A--A--T--T--T--A--A--(CH.sub.2).sub.n Z), d (T--T--T--A--A--T--T--T--A--A--T--T--T--A--A--(CH.sub.2).sub.n Z), and d (T--T--T--T--T--T--T--A--(CH.sub.2).sub.n Z), wherein: T-- is thymidine linked through a phosphodiester bond, A-- is adenosine linked through a phosphodiester bond, C-- is cytidine linked through a phosphodiester bond, G-- is guanidine linked through a phosphodiester bond, n is an integer from 1 to 25, and Z represents an intercalating agent selected from acridine, furocoumarin, ##STR88## and derivatives of said intercalating agents.

Claim 8

Dependent Claim 115 words

An oligonucleotide or an oligodeoxynucleotide comprising a natural or modified chain of nucleotides or deoxynucleotides to which an intercalating group is attached via a covalent bond having the sequence selected from the group consisting of: d (A--T--A--A--A--T--T--C--A--C--(CH.sub.2).sub.n Z, d (A--A--T--G--G--T--A--A--A--A--T--(CH.sub.2).sub.n Z), d (T--T--C--T--C--C--C--C--C--A--C--C--A--(CH.sub.2).sub.n Z), d (T--T--T--A--A--(CH.sub.2).sub.n Z), d (T--T--T--A--A--T--T--T--A--A--(CH.sub.2).sub.n Z), d (T--T--T--A--A--T--T--T--A--A--T--T--T--A--A--(CH.sub.2).sub.n Z), and d (T--T--T--T--T--T--T--A--(CH.sub.2).sub.n Z), wherein: T-- is thymidine linked through a phosphodiester bond, A-- is adenosine linked through a phosphodiester bond, C-- is cytidine linked through a phosphodiester bond, G-- is guanidine linked through a phosphodiester bond, n is an integer from 1 to 25, and Z represents an intercalating agent selected from acridine, furocoumarin, ##STR88## and derivatives of said intercalating agents.

Claim 9

Dependent Claim 106 words

An oligonucleotide or oligodeoxynucleotide comprising a chain of natural or modified nucleotides or deoxynucleotides to which an intercalating group is attached via a covalent bond having the formula: ##STR89## wherein T is thymine T-- and --T are thymidine linked through a phosphodiester bond, A is adenine, C is cytosine, G is guanine, U is uracil, ∓T and T∓ represent thymidine linked through a a phosphotriester bond wherein each phosphate is protected by a p-chlorophenyl group, A-- is adenosine linked through a phosphodiester bond, C-- is cytidine linked through a phosphodiester bond, G-- is guanosine linked through a phosphodiester bond, Z' is ##STR90## and Z" is ##STR91##

Claim 10

Dependent Claim 106 words

An oligonucleotide or oligodeoxynucleotide comprising a chain of natural or modified nucleotides or deoxynucleotides to which an intercalating group is attached via a covalent bond having the formula: ##STR89## wherein T is thymine T-- and --T are thymidine linked through a phosphodiester bond, A is adenine, C is cytosine, G is guanine, U is uracil, ∓T and T∓ represent thymidine linked through a a phosphotriester bond wherein each phosphate is protected by a p-chlorophenyl group, A-- is adenosine linked through a phosphodiester bond, C-- is cytidine linked through a phosphodiester bond, G-- is guanosine linked through a phosphodiester bond, Z' is ##STR90## and Z" is ##STR91##

Claim 11

Dependent Claim 29 words

The oligonucleotide or oligodeoxynucleotide according to claim 6, wherein said oligonucleotide or oligodeoxynucleotide is in the form of an optically pure R or S isomer or a mixture thereof.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1992-05-29	1992-11-28	1993-05-30	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1996-05-29	1996-11-28	1997-05-30	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2000-05-29	2000-11-28	2001-05-30	$7700.00	Window Closed / Lapsed

Novel compounds containing an oligonucleotide sequence bonded to an intercalating agent, a process for their synthesis and their use

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