# US 8,569,262 B2 · Polysaccharide compositions and methods of use for the treatment and prevention of disorders associated with progenitor cell mobilization > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,569,262 B2 - Document ID: US8569262B2 - Status: Granted - Kind: B2 - Application number: 12/816,369 - Filed: 2010-06-15 - Published: 2010-12-16 - Granted: 2013-10-29 - Earliest claimed: 2007-11-02 - Assignees: Momenta Pharmaceuticals, Inc. - Applicants: Mallikarjun Sundaram; Takashi Kei Kishimoto; Sucharita Roy - Inventors: Mallikarjun Sundaram; Takashi Kei Kishimoto; Sucharita Roy - Web page: https://patentgrep.com/patent/US8569262B2 ## CPC - A61K 31/727: Heparin; Heparan - A61K 31/404: Indoles, e.g. pindolol - A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid - A61K 33/243: Platinum; Compounds thereof - A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - C08B 37/0078: {Degradation products} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21) ## Abstract Polysaccharide preparations lacking substantial anticoagulant activity are provided herein. Methods of making and using such preparations are provided. ## Claims ### Claim 1 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. ### Claim 2 (depends on 1) The method of claim 1, wherein the polysaccharide preparation has an anti-Xa activity of less than 15 IU/mg. ### Claim 3 (depends on 1) The method of claim 1, wherein the polysaccharide preparation has an anti-Xa activity of less than 10 IU/mg. ### Claim 4 (depends on 1) The method of claim 1, wherein the preparation has greater than 5% and less than 20% glycol split uronic acid residues. ### Claim 5 (depends on 1) The method of claim 1, wherein the preparation has between 10% and 20% glycol split uronic acid residues. ### Claim 6 (depends on 1) The method of claim 1, wherein the preparation has greater than 40% U2SHNS,6S disaccharide residues. ### Claim 7 (depends on 6) The method of claim 6, wherein the preparation has greater than 70% U2SHNS,6S disaccharide residues. ### Claim 8 (depends on 6) The method of claim 6, wherein the preparation has a degree of desulfation less than 40%. ### Claim 9 (depends on 6) The method of claim 6, wherein the preparation has a degree of desulfation less than 30%. ### Claim 10 (depends on 6) The method of claim 6, wherein the preparation has a degree of desulfation less than 10%. ### Claim 11 (depends on 1) The method of claim 1, wherein the reducing end further comprises a 2,5-anhydromannitol residue. ### Claim 12 (depends on 1) The method of claim 1, wherein the polysaccharides of the preparation have a uronic acid at the non-reducing end. ### Claim 13 (depends on 1) The method of claim 1, wherein the polysaccharides of the preparation have a non native uronic acid at the non-reducing end. ### Claim 14 (depends on 1) The method of claim 1, wherein the polysaccharides of the preparation have a glycol split uronic acid at the non-reducing end. ### Claim 15 (depends on 1) The method of claim 1, wherein n=1-3. ### Claim 16 (depends on 1) The method of claim 1, wherein the pancreatic cancer is a metastatic cancer. ### Claim 17 (depends on 1) The method of claim 1, wherein the preparation is administered intravenously. ### Claim 18 (depends on 1) The method of claim 1, wherein the preparation is administered subcutaneously. ### Claim 19 (depends on 1) The method of claim 1, wherein the preparation is administered daily. ### Claim 20 (depends on 1) The method of claim 1, wherein the preparation is administered in combination with a second therapy. ### Claim 21 (depends on 20) The method of claim 20, wherein the second therapy comprises administration of one or more therapeutic agents. ### Claim 22 (depends on 21) The method of claim 21, wherein the therapeutic agent is a cytotoxic or cytostatic agent or a combination thereof. ### Claim 23 (depends on 21) The method of claim 21, wherein the one or more therapeutic agent is gemcitabine. ### Claim 24 (depends on 23) The method of claim 23, further comprising administering abraxane in combination with the polysaccharide preparation and the gemcitabine. ### Claim 25 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. ### Claim 26 (depends on 25) The method of claim 25, wherein the polysaccharide preparation has an anti-Xa activity of less than 15 IU/mg. ### Claim 27 (depends on 25) The method of claim 25, wherein the polysaccharide preparation has an anti-Xa activity of less than 10 IU/mg. ### Claim 28 (depends on 25) The method of claim 25, wherein the plurality of polysaccharide chains of the preparation each have no more than 2 glycol split uronic acid residues (UG). ### Claim 29 (depends on 28) The method of claim 28, wherein the plurality of polysaccharide chains of the preparation each have no more than 1 glycol split uronic acid residue (UG) per polysaccharide chain. ### Claim 30 (depends on 25) The method of claim 25, wherein the reducing end further comprises a 2,5-anhydromannitol residue. ### Claim 31 (depends on 25) The method of claim 25, wherein the polysaccharides of the preparation have a uronic acid at the non-reducing end. ### Claim 32 (depends on 25) The method of claim 25, wherein the polysaccharides of the preparation have a non native uronic acid at the non-reducing end. ### Claim 33 (depends on 25) The method of claim 25, wherein the polysaccharides of the preparation have a glycol split uronic acid at the non-reducing end. ### Claim 34 (depends on 25) The method of claim 25, wherein n=1-3. ### Claim 35 (depends on 25) The method of claim 25, wherein the pancreatic cancer is a metastatic cancer. ### Claim 36 (depends on 25) The method of claim 25, wherein the preparation is administered intravenously. ### Claim 37 (depends on 25) The method of claim 25, wherein the preparation is administered subcutaneously. ### Claim 38 (depends on 25) The method of claim 25, wherein the preparation is administered daily. ### Claim 39 (depends on 25) The method of claim 25, wherein the preparation is administered in combination with a second therapy. ### Claim 40 (depends on 39) The method of claim 39, wherein the second therapy comprises administration of one or more therapeutic agents. ### Claim 41 (depends on 40) The method of claim 40, wherein the therapeutic agent is a cytotoxic or cytostatic agent or a combination thereof. ### Claim 42 (depends on 40) The method of claim 40, wherein the one or more therapeutic agent comprises gemcitabine. ### Claim 43 (depends on 42) The method of claim 42, further comprising administering abraxane in combination with the polysaccharide preparation and the gemcitabine. ### Claim 44 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. ### Claim 45 (depends on 44) The method of claim 44, further comprising administering the pharmaceutical composition in combination with gemcitabine. ### Claim 46 (depends on 45) The method of claim 45, further comprising administering abraxane in combination with the gemcitabine.