US5032679A — Heparin fragments as inhibitors of smooth muscle …

Claim 1

Independent Claim 83 words

A process to prepare a glycosaminoglycoside (GAG) composition useful in preventing or inhibiting the proliferation of smooth muscle cells which method comprises: separating a mixture obtainable by complete nitrous acid depolymerization of mammalian heparin/heparan sulfate into fragments according to molecular size, and recovering the size fraction of the mixture comprised predominantly of fragments which are tetrasaccharide units, the mixture of fragments having a lower antithrombotic activity and a higher activity for inhibiting the proliferation of smooth muscle cells as compared with commercial heparin.

Claim 2

Dependent Claim 83 words

A process to prepare a glycosaminoglycoside (GAG) composition useful in preventing or inhibiting the proliferation of smooth muscle cells which method comprises: separating a mixture obtainable by complete nitrous acid depolymerization of mammalian heparin/heparan sulfate into fragments according to molecular size, and recovering the size fraction of the mixture comprised predominantly of fragments which are tetrasaccharide units, the mixture of fragments having a lower antithrombotic activity and a higher activity for inhibiting the proliferation of smooth muscle cells as compared with commercial heparin.

Claim 3

Dependent Claim 14 words

The process of claim 1 wherein the heparin/heparan sulfate is depolymerized with nitrous acid.

Claim 4

Dependent Claim 14 words

The process of claim 1 wherein the depolymerized fragments are separated using gel filtration.

Claim 5

Dependent Claim 23 words

The process of claim 3 wherein gel filtration is conducted using a column containing Biogel P2, and eluting with 15% V/V acetic acid.

Claim 6

Dependent Claim 10 words

A GAG composition prepared by the process of claim 1.

Claim 7

Dependent Claim 9 words

The GAG composition of claim 5 conjugated to label.

Claim 8

Dependent Claim 38 words

A pharmaceutical composition useful in the treatment of conditions characterized by unwanted smooth muscle cell proliferation, which composition comprises an effective amount of the GAG composition of claim 5 in admixture with at least one pharmaceutically acceptable excipient.

Claim 9

Dependent Claim 39 words

A method to treat a condition characterized by unwanted smooth muscle cell proliferation, which method comprises administering to a subject in need of such treatment an effective amount of the composition of claim 5 or a pharmaceutical composition thereof.

Claim 10

Dependent Claim 15 words

The method of claim 8 wherein the condition is a result of surgery or trauma.

Claim 11

Dependent Claim 30 words

The method of claim 8 wherein the condition is selected from the group consisting of Goodpasture's syndrome, acute glomerulonephritis, neonatal pulmonary hypertension, asthma, acute pulmonary hypertension and renal vascular hypertension.

Claim 12

Dependent Claim 11 words

The method of claim 8 wherein the composition is administered intravenously.

Claim 13

Dependent Claim 17 words

The method of claim 9 wherein the composition is administered topically or at the location of trauma.

Claim 14

Dependent Claim 44 words

A method to diagnose a deficiency or excess in antiproliferative oligosaccharides in a mammalian subject which method comprises assessing in a biological sample taken from the subject the level of oligosaccharide competitive in an immunoassay with the composition of claim 5 in labeled form.

Claim 15

Dependent Claim 103 words

A compound obtainable by isolation from depolymerized heparin which is a hexasaccharide or tetrasaccharide, or salt thereof, capable of preventing or inhibiting the proliferation of smooth muscle cells, the compound having a lower antithrombotic activity and a higher activity for inhibiting the proliferation of smooth muscle cells as compared with commercial heparin, wherein the compound has the following structural formula: ##STR5## wherein n is 1 or 2, R is H or a cation, X is H or SO 3 R and Ac is acyl (2-5C), and * indicates that the associated C (carbon 5) can be in either the R or S configuration.

Claim 16

Dependent Claim 103 words

A compound obtainable by isolation from depolymerized heparin which is a hexasaccharide or tetrasaccharide, or salt thereof, capable of preventing or inhibiting the proliferation of smooth muscle cells, the compound having a lower antithrombotic activity and a higher activity for inhibiting the proliferation of smooth muscle cells as compared with commercial heparin, wherein the compound has the following structural formula: ##STR5## wherein n is 1 or 2, R is H or a cation, X is H or SO 3 R and Ac is acyl (2-5C), and * indicates that the associated C (carbon 5) can be in either the R or S configuration.

Claim 17

Dependent Claim 7 words

The compound of claim 14 wherein n=1.

Claim 18

Dependent Claim 14 words

The compound of claim 14 which is selected from the group consisting of: ##STR6##

Claim 19

Dependent Claim 80 words

The compound isolable from digested heparin which compound has a higher activity for preventing or inhibiting the proliferation of smooth muscle cells and a lower antithrombotic activity as compared with commercial heparin, which compound has the formula: ##STR7## wherein n is 1 or 2, R is H or a cation, X is H or SO 3 R and Ac is acyl (2-5C) and * indicates that the associated C (carbon 5) can be in either the R or S configuration.

Claim 20

Dependent Claim 80 words

The compound isolable from digested heparin which compound has a higher activity for preventing or inhibiting the proliferation of smooth muscle cells and a lower antithrombotic activity as compared with commercial heparin, which compound has the formula: ##STR7## wherein n is 1 or 2, R is H or a cation, X is H or SO 3 R and Ac is acyl (2-5C) and * indicates that the associated C (carbon 5) can be in either the R or S configuration.

Claim 21

Dependent Claim 14 words

The compound of claim 17 wherein the reducing or non-reducing terminal sugar is deleted.

Claim 22

Dependent Claim 7 words

The compound of claim 17 wherein n=1.

Claim 23

Dependent Claim 14 words

The compound of claim 17 which is selected from the group consisting of: ##STR8##

Claim 24

Dependent Claim 37 words

A pharmaceutical composition useful in the treatment of conditions characterized by unwanted smooth muscle cell proliferation, which composition comprises an effective amount of the compound of claim 14 in admixture with at least one pharmaceutically acceptable excipient.

Claim 25

Dependent Claim 39 words

A method to treat a condition characterized by unwanted smooth muscle cell proliferation, which method comprises administering to a subject in need of such treatment an effective amount of the compound of claim 14 or a pharmaceutical composition thereof.

Claim 26

Dependent Claim 15 words

The method of claim 22 wherein the condition is a result of surgery or trauma.

Claim 27

Dependent Claim 17 words

The method of claim 23 wherein the compound is administered topically or at the location of trauma.

Claim 28

Dependent Claim 11 words

The method of claim 22 wherein the compound is administered intravenously.

Claim 29

Dependent Claim 30 words

The method of claim 22 wherein the condition is selected from the group consisting of Goodpasture's syndrome, acute glomerulonephritis, neonatal pulmonary hypertension, asthma, actue pulmonary hypertension and renal vascular hypertension.

Claim 30

Dependent Claim 44 words

A method to diagnose a deficiency or excess in antiproliferative GAG in a mammalian subject which method comprises assessing in a biological sample taken from the subject the level of GAG competitive in an immunoassay with the compound of claim 14 in labeled form.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1994-07-15	1995-01-14	1995-07-16	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1998-07-15	1999-01-14	1999-07-16	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2002-07-15	2003-01-14	2003-07-16	$7700.00	Window Closed / Lapsed

Heparin fragments as inhibitors of smooth muscle cell proliferation

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