Analysis of sulfated polysacchrides

Abstract

The invention relates to methods and products associated with analyzing and monitoring heterogeneous populations of sulfated polysaccharides. In particular therapeutic heparin products including low molecular weight heparin products and methods of analyzing and monitoring these products are described.

1 . A method of analyzing a sample comprising a composition which includes a polysaccharide, the method comprising providing a structural signature for the composition, thereby analyzing the composition. 
     
     
         2 .- 20 . (canceled) 
     
     
         21 . A method for determining bioequivalence comprising the steps of:
 a. providing or determining the structural signature of a first composition;   b. providing or determining the bioavailability of the first composition;   c. providing or determining the structural signature of a second composition;   d. providing or determining the bioavailability of the second composition; and   e. comparing the structural compositions and bioavailability of the first and second compositions;   thus determining the bioequivalence of the compositions.   
     
     
         22 .- 23 . (canceled) 
     
     
         24 . A method of analyzing a polysaccharide drug, the method comprising:
 a. determining a first structural signature for a first batch of drug having a first level of preselected patient reaction;   b. determining a second structural signature, for a second batch of drug having a second level of preselected patient reaction; and   c. comparing the first and second structural signature determinations to determine the presence or absence of a correlation between a property of the drug with a preselected level of patient reaction.   
     
     
         25 .- 103 . (canceled) 
     
     
         104 . A method of analyzing a sample of LMWH comprising the steps of:
 d. providing the sample; and   e. determining if a non-natural sugar, e.g., a modified sugar, is present in the sample;   thereby analyzing the sample.   
     
     
         105 .- 106 . (canceled) 
     
     
         107 . The method of  claim 104  wherein the non-natural sugar comprises peak 10. 
     
     
         108 . The method of  claim 104  wherein the non-natural sugar comprises peak 11. 
     
     
         109 .- 127 . (canceled) 
     
     
         128 . A method of analyzing a sample or a subject the method comprising the steps of:
 a. providing a sample;   b. determining if one or more components chosen from the group consisting of −UH NAc,6S GH NS,3S,6S ; −UH NS,6S GH NS,3S,6S ; −UH NAc,6S GH NS,3S ; −UH NS,6S GH NS,3S  or a fragment or fragments thereof is present in the sample; and   c. optionally, measuring the level of the component or components;   thereby monitoring the subject.   
     
     
         129 .- 240 . (canceled) 
     
     
         241 . A LMWH preparation having an increased or decreased ratio of anti-IIa activity and anti-Xa activity. 
     
     
         242 .- 261 . (canceled) 
     
     
         262 . A method of inhibiting coagulation in a patient, comprising administering one or more doses of a therapeutic amount of a LMWH preparation of  claim 241  having high anti-Xa and anti-IIa activity, monitoring the status of the subject, then administering one or more doses of a therapeutic amount of a LMWH preparation of  claim 241  having high anti-Xa activity and anti-IIa activity alone. 
     
     
         263 .- 265 . (canceled) 
     
     
         266 . A LMWH composition having both anti-Xa and anti-IIa activity comprising less than or equal to 20% <2000 Da species, greater than or equal to 68% 2000-8000 Da species, and less than or equal to 18% >8000 Da species, preferably with an average molecular weight of about 4500 Da, wherein the anti-Xa activity is >50% neutralizable by protamine and the anti-IIa activity is >70% neutralizable by protamine. 
     
     
         267 .- 306 . (canceled) 
     
     
         307 . A method for determining the safety or suitability of a heparin for use in a particular indication, comprising the steps of:
 a. providing the structural signature of the heparin;   b. providing a reference structural signature;   c. determining if the heparin is acceptable.   
     
     
         308 .- 309 . (canceled)