US 2013/0156698 A1Published application

Tissue targeting

AssigneeMomenta Pharmaceuticals, Inc.

InventorsHe Zhou, Edward Cochran, Takashi Kei Kishimoto

Life of this patent

Estimating the term…

Abstract

Methods and compositions related to targeting agents to tumor tissue are described.

Claims24

Dependent claims

A method of targeting a therapeutic or imaging agent to a tumor tissue of a patient, the method comprising (a) identifying a patient with a tumor tissue, wherein the patient is in need of administration of a therapeutic or imaging agent to treat or image the tumor;

(b) providing a conjugate of the therapeutic or imaging agent and a LMWH composition;
and (c) administering the conjugate to the patient, wherein the LMWH is selected from the group consisting of:
(a) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 8,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) greater than 5% and less than 50% glycol split uronic acid residues;
(b) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
(iii) a polysaccharide chain having a glycol split uronic acid residue (UG);
and
(iv) polysaccharide chains each having no more than 3 glycol split uronic acid residues (UG);
(c) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) polysaccharide chains having on average between 0.2 and 3 glycol split uronic acid residues (UG) per polysaccharide chain;
(d) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) polysaccharide chains having greater than 40% U2SHNS,6S disaccharide residues;
(e) a LMWH having the following characteristics:
a polysaccharide preparation lacking substantial anticoagulant activity, wherein the preparation consists essentially of polysaccharides that include Formula I:
[Uw-Hx,y,z]m{tilde over ( )}[UG-Hx,y,z]n
wherein U indicates a uronic acid residue and H indicates a hexosamine residue;
wherein m and n are integers such that
m=4-16, and
n=1-4:
w=−2OS or −2OH;
x=—NS or —NAc;
y=−3OS or −3OH;
z=−6OS or −6OH;
and
wherein the symbol {tilde over ( )} indicates that the units marked m and n are distributed along the polysaccharide chain and are not necessarily in sequence, wherein w, x, y, and z are each the same or different on each unit marked m, and wherein x, y, and z are each the same or different on each unit marked n;
(f) a LMWH having the following characteristics:
lacks substantial anticoagulant activity, has antimetastatic activity and consists essentially of polysaccharides that include Formula II:
[Uw-Hx,y,z]m-[UG-Hx,y,z]n-[Uw-Hx,y,z]o-[UG-Hx,y,z]p-[Uw-Hx,y,z]q
wherein U indicates a uronic acid residue and H indicates a hexosamine residue;
wherein m-q are integers such that:
m=0-10;
n=0-3.
o=0-10;
p=0-3;
q=0-10;
w, for each occurrence, is independently −2OS or −2OH;
x, for each occurrence, is independently —NS or —NAc;
y, for each occurrence, is independently −3OS or −3OH;
z, for each occurrence, is independently −6OS or −6OH;
and UG=;
wherein w, x, y, and z are each the same or different on each unit marked m, n, o, p, or q, to thereby target the agent to the tumor tissue.

49 more elements

A method of treating a subject, the method comprising:

(a) identifying a subject who has a tumor, and
(b) administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a conjugate of an anti-tumor agent and a LMWH composition, wherein the LMWH is selected from the group consisting of:
(a) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 8,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) greater than 5% and less than 50% glycol split uronic acid residues;
(b) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
(iii) a polysaccharide chain having a glycol split uronic acid residue (UG);
and
(iv) polysaccharide chains each having no more than 3 glycol split uronic acid residues (UG);
(c) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) polysaccharide chains having on average between 0.2 and 3 glycol split uronic acid residues (UG) per polysaccharide chain;
(d) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) polysaccharide chains having greater than 40% U2SHNS,6S disaccharide residues;
(e) a LMWH having the following characteristics:
a polysaccharide preparation lacking substantial anticoagulant activity, wherein the preparation consists essentially of polysaccharides that include Formula I:
[Uw-Hx,y,z]m{tilde over ( )}[UG-Hx,y,z]n
wherein U indicates a uronic acid residue and H indicates a hexosamine residue;
wherein m and n are integers such that
m=4-16, and
n=1-4:
w=−2OS or −2OH;
x=—NS or —NAc;
y=−3OS or −3OH;
z=−6OS or −6OH;
and
wherein the symbol {tilde over ( )} indicates that the units marked m and n are distributed along the polysaccharide chain and are not necessarily in sequence, wherein w, x, y, and z are each the same or different on each unit marked m, and wherein x, y, and z are each the same or different on each unit marked n;
(f) a LMWH having the following characteristics:
lacks substantial anticoagulant activity, has antimetastatic activity and consists essentially of polysaccharides that include Formula II:
[Uw-Hx,y,z]m-[UG-Hx,y,z]n-[Uw-Hx,y,z]o-[UG-Hx,y,z]p-[Uw-Hx,y,z]q
wherein U indicates a uronic acid residue and H indicates a hexosamine residue;
wherein m-q are integers such that:
m=0-10;
n=0-3.
o=0-10;
p=0-3;
q=0-10;
w, for each occurrence, is independently −2OS or −2OH;
x, for each occurrence, is independently —NS or —NAc;
y, for each occurrence, is independently −3OS or −3OH;
z, for each occurrence, is independently −6OS or −6OH;
and
wherein w, x, y, and z are each the same or different on each unit marked m, n, o, p, or q.

49 more elements

A pharmaceutical composition comprising a conjugate of a therapeutic or imaging agent and a LMWH composition, wherein the LMWH is selected from the group consisting of:

(a) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 8,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) greater than 5% and less than 50% glycol split uronic acid residues;
(b) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
(iii) a polysaccharide chain having a glycol split uronic acid residue (UG);
and
(iv) polysaccharide chains each having no more than 3 glycol split uronic acid residues (UG);
(c) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) polysaccharide chains having on average between 0.2 and 3 glycol split uronic acid residues (UG) per polysaccharide chain;
(d) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) polysaccharide chains having greater than 40% U2SHNS,6S disaccharide residues;
(e) a LMWH having the following characteristics:
a polysaccharide preparation lacking substantial anticoagulant activity, wherein the preparation consists essentially of polysaccharides that include Formula I:
[Uw-Hx,y,z]m{tilde over ( )}[UG-Hx,y,z]n
wherein U indicates a uronic acid residue and H indicates a hexosamine residue;
wherein m and n are integers such that
m=4-16, and
n=1-4:
w=−2OS or −2OH;
x=—NS or —NAc;
y=−3OS or −3OH;
z=−6OS or −6OH;
and
wherein the symbol {tilde over ( )} indicates that the units marked m and n are distributed along the polysaccharide chain and are not necessarily in sequence, wherein w, x, y, and z are each the same or different on each unit marked m, and wherein x, y, and z are each the same or different on each unit marked n;
(f) a LMWH having the following characteristics:
lacks substantial anticoagulant activity, has antimetastatic activity and consists essentially of polysaccharides that include Formula II:
[Uw-Hx,y,z]m-[UG-Hx,y,z]n-[Uw-Hz,y,z]o-[UG-Hx,y,z]p-[Uw-Hx,y,z]q
wherein U indicates a uronic acid residue and H indicates a hexosamine residue;
wherein m-q are integers such that:
m=0-10;
n=0-3.
o=0-10;
p=0-3;
q=0-10;
w, for each occurrence, is independently −2OS or −2OH;
x, for each occurrence, is independently —NS or —NAc;
y, for each occurrence, is independently −3OS or −3OH;
z, for each occurrence, is independently −6OS or −6OH;
and
wherein w, x, y, and z are each the same or different on each unit marked m, n, o, p, or q.

47 more elements

A method of targeting a therapeutic or imaging agent to a fibrotic tissue or inflammatory lesion of a patient, the method comprising (a) identifying a patient with a fibrotic tissue or inflammatory lesion, wherein the patient is in need of administration of a therapeutic or imaging agent to treat or image the fibrotic tissue or inflammatory lesion;

(b) providing a conjugate of the therapeutic or imaging agent and a LMWH composition;
and (c) administering the conjugate to the patient, wherein the LMWH is selected from the group consisting of:
(a) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 8,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) greater than 5% and less than 50% glycol split uronic acid residues;
(b) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
(iii) a polysaccharide chain having a glycol split uronic acid residue (UG);
and
(iv) polysaccharide chains each having no more than 3 glycol split uronic acid residues (UG);
(c) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) polysaccharide chains having on average between 0.2 and 3 glycol split uronic acid residues (UG) per polysaccharide chain;
(d) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) polysaccharide chains having greater than 40% U2SHNS,6S disaccharide residues;
(e) a LMWH having the following characteristics:
a polysaccharide preparation lacking substantial anticoagulant activity, wherein the preparation consists essentially of polysaccharides that include Formula I:
[Uw-Hx,y,z]m{tilde over ( )}[UG-Hx,y,z]n
wherein U indicates a uronic acid residue and H indicates a hexosamine residue;
wherein m and n are integers such that
m=4-16, and
n=1-4:
w=−2OS or −2OH;
x=—NS or —NAc;
y=−3OS or −3OH;
z=−6OS or −6OH;
and
wherein the symbol {tilde over ( )} indicates that the units marked m and n are distributed along the polysaccharide chain and are not necessarily in sequence, wherein w, x, y, and z are each the same or different on each unit marked m, and wherein x, y, and z are each the same or different on each unit marked n;
(f) a LMWH having the following characteristics:
lacks substantial anticoagulant activity, has antimetastatic activity and consists essentially of polysaccharides that include Formula II:
[Uw-Hx,y,z]m-[UG-Hx,y,z]n-[Uw-Hx,y,z]o-[UG-Hx,y,z]p-[Uw-Hx,y,z]q
wherein U indicates a uronic acid residue and H indicates a hexosamine residue;
wherein m-q are integers such that:
m=0-10;
n=0-3.
o=0-10;
p=0-3;
q=0-10;
w, for each occurrence, is independently −2OS or −2OH;
x, for each occurrence, is independently —NS or —NAc;
y, for each occurrence, is independently −3OS or −3OH;
z, for each occurrence, is independently −6OS or −6OH;
and
wherein w, x, y, and z are each the same or different on each unit marked m, n, o, p, or q, to thereby target the agent to the fibrotic tissue or inflammatory lesion.

49 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/641,278Filed 15 Apr 2011
Priority: 16 Apr 2010
Published: 20 Jun 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification18 codes

A61K 51/065
Macromolecular compounds , carriers being organic macromolecular compounds, i.e. organic oligomeric, polymeric, dendrimeric molecules: conjugates…
A61K 31/00
Medicinal preparations containing organic active ingredients
A61K 31/727
Glycosaminoglycans, i.e. mucopolysaccharides: heparin; Heparan
A61K 47/61
The modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule: the organic macromolecular…

Family

Application61/325,146Us provisional application · filed 16 Apr 2010
US 9,387,256 B2Related patent
US 2013/0156698 A1This patent

From the US filing history. Foreign family members aren’t listed.

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(b) providing a conjugate of the therapeutic or imaging agent and a LMWH composition;
and (c) administering the conjugate to the patient, wherein the LMWH is selected from the group consisting of:
(a) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 8,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) greater than 5% and less than 50% glycol split uronic acid residues;
(b) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
(iii) a polysaccharide chain having a glycol split uronic acid residue (UG);
and
(iv) polysaccharide chains each having no more than 3 glycol split uronic acid residues (UG);
(c) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) polysaccharide chains having on average between 0.2 and 3 glycol split uronic acid residues (UG) per polysaccharide chain;
(d) a LMWH having the following characteristics:
(i) a weight average chain molecular weight between 3,500 and 7,000 Da;
(ii) anti-Xa activity and anti-IIa activity each less than 50 IU/mg;
and
(iii) polysaccharide chains having greater than 40% U2SHNS,6S disaccharide residues;
(e) a LMWH having the following characteristics:
a polysaccharide preparation lacking substantial anticoagulant activity, wherein the preparation consists essentially of polysaccharides that include Formula I:
[Uw-Hx,y,z]m{tilde over ( )}[UG-Hx,y,z]n
wherein U indicates a uronic acid residue and H indicates a hexosamine residue;
wherein m and n are integers such that
m=4-16, and
n=1-4:
w=−2OS or −2OH;
x=—NS or —NAc;
y=−3OS or −3OH;
z=−6OS or −6OH;
and
wherein the symbol {tilde over ( )} indicates that the units marked m and n are distributed along the polysaccharide chain and are not necessarily in sequence, wherein w, x, y, and z are each the same or different on each unit marked m, and wherein x, y, and z are each the same or different on each unit marked n;
(f) a LMWH having the following characteristics:
lacks substantial anticoagulant activity, has antimetastatic activity and consists essentially of polysaccharides that include Formula II:
[Uw-Hx,y,z]m-[UG-Hx,y,z]n-[Uw-Hx,y,z]o-[UG-Hx,y,z]p-[Uw-Hx,y,z]q
wherein U indicates a uronic acid residue and H indicates a hexosamine residue;
wherein m-q are integers such that:
m=0-10;
n=0-3.
o=0-10;
p=0-3;
q=0-10;
w, for each occurrence, is independently −2OS or −2OH;
x, for each occurrence, is independently —NS or —NAc;
y, for each occurrence, is independently −3OS or −3OH;
z, for each occurrence, is independently −6OS or −6OH;
and UG=;
wherein w, x, y, and z are each the same or different on each unit marked m, n, o, p, or q, to thereby target the agent to the tumor tissue.

49 more elements

Facts

Application

13/641,278Filed 15 Apr 2011

Priority

16 Apr 2010

Published

20 Jun 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification18 codes

A61K 51/065
Macromolecular compounds , carriers being organic macromolecular compounds, i.e. organic oligomeric, polymeric, dendrimeric molecules: conjugates…
A61K 31/00
Medicinal preparations containing organic active ingredients
A61K 31/727
Glycosaminoglycans, i.e. mucopolysaccharides: heparin; Heparan
A61K 47/61
The modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule: the organic macromolecular…