Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization
AssigneeMomenta Pharmaceuticals, Inc.
InventorsMallikarjun Sundaram, Takashi Kei Kishimoto, Sucharita Roy
Life of this patent
Estimating the term…
Abstract
Polysaccharide preparations lacking substantial anticoagulant activity are provided herein. Methods of making and using such preparations are provided.
Claims46
A method of lessening, reducing, mitigating, ameliorating, or delaying pancreatic cancer in a subject, comprising administering to the subject a pharmaceutical composition comprising a polysaccharide preparation having the following characteristics:
- (a) a weight average chain molecular weight between 3,500 and 8,000 Da;
- (b) anti-Xa activity of less than 20 IU/mg and anti-IIa activity of 1 IU/mg or less;
- (c) greater than 5% and less than 25% glycol split uronic acid residues;
- and
- (d) a molecular weight distribution such that 10-40% of the polysaccharides of the preparation have a molecular weight <3000 Da;
- 45-65% of the polysaccharides have a molecular weight between 3000-8000 Da, and 15-30% of the polysaccharides have a molecular weight >8000 Da, wherein, the preparation comprises polysaccharides of Formula I:
- [Uw-Hx,y,z]m˜[UG-Hx,y,z]n
- wherein each occurrence of U indicates a uronic acid residue and each occurrence of H indicates a hexosamine residue;
- wherein m and n are integers such that
- m=4-16, and
- n=1-4;
- each of w, x, y and z can independently be the same or different for each occurrence of [Uw-Hx,y,z] and each of x, y and z can independently be the same or different for each occurrence of [UG-Hx,y,z], wherein
- w=-2OS or -2OH;
- x=—NS or —NAc;
- y=-3OS or -3OH;
- z=-6OS or -6OH;
- and
- wherein the symbol ˜ indicates that the units marked m and n are distributed along the polysaccharide chain and are not necessarily in sequence.
A method of lessening, reducing, mitigating, ameliorating, or delaying pancreatic cancer in a subject, the method comprising administering a polysaccharide preparation having anti-Xa activity of less than 20 IU/mg and anti-IIa activity of 1 IU/mg or less;
- greater than 5% and less than 25% glycol split uronic acid residues;
- a plurality of polysaccharide chains of the preparation having a glycol split uronic acid residue (UG), wherein, the plurality of polysaccharide chains of the preparation each have no more than 3 glycol split uronic acid residues (UG);
- and the polysaccharide preparation has a molecular weight distribution such that 10-40% of the oligosaccharides of the preparation have a molecular weight <3000 Da;
- 45-65% of the oligosaccharides have a molecular weight between 3000-8000 Da, and 15-30% of the oligosaccharides have a molecular weight >8000 Da, wherein, the preparation comprises polysaccharides of Formula I:
- [Uw-Hx,y,z]m˜[UG-Hx,y,z]n
- wherein each occurrence of U indicates a uronic acid residue and each occurrence of H indicates a hexosamine residue;
- wherein m and n are integers such that
- m=4-16, and
- n=1-4:
- each of w, x, y and z can independently be the same or different for each occurrence of [Uw-Hx,y,z] and each of x, y and z can independently be the same or different for each occurrence of [UG-Hx,y,z], wherein
- w=-2OS or -2OH;
- x=—NS or —NAc;
- y=-3OS or -3OH;
- z=-6OS or -6OH;
- and
- wherein the symbol ˜ indicates that the units marked m and n are distributed along the polysaccharide chain and are not necessarily in sequence.
A method of lessening, reducing, mitigating, ameliorating, or delaying pancreatic cancer in a subject, comprising administering to the subject a pharmaceutical composition comprising a polysaccharide preparation having the following characteristics:
- (a) a weight average chain molecular weight between 3,500 and 8,000 Da;
- (b) a molecular weight distribution such that 10-40% of the polysaccharides of the preparation have a molecular weight <3000 Da;
- 45-65% of the polysaccharides have a molecular weight between 3000-8000 Da, and 15-30% of the polysaccharides have a molecular weight >8000 Da;
- (c) greater than 5% and less than 25% glycol split uronic acid residues;
- (d) anti-Xa activity of less than 15 IU/mg and anti-IIa activity of 1 IU/mg or less, wherein, the preparation comprises polysaccharides of Formula I:
- [Uw-Hx,y,z]m˜[UG-Hx,y,z]n
- wherein each occurrence of U indicates a uronic acid residue and each occurrence of H indicates a hexosamine residue;
- wherein m and n are integers such that
- m=4-16, and
- n=1-3;
- each of w, x, y and z can independently be the same or different for each occurrence of [Uw-Hx,y,z] and each of x, y and z can independently be the same or different for each occurrence of [UG-Hx,y,z], wherein
- w=-2OS or -2OH;
- x=—NS or —NAc;
- y=-3OS or -3OH;
- z=-6PS or -6OH;
- and
- wherein the symbol ˜ indicates that the units marked m and n are distributed along the polysaccharide chain and are not necessarily in sequence;
- and
- wherein a plurality of the polysaccharides on the preparation have a 2,5-anhydromannitol residue at the reducing end and non native uronic acid at the non-reducing end.
Dependencies are inferred from the claim text.