CA2525399A1 - Novel spacer moiety for poly(ethylene glycol)-modified peptide-based co mpounds - Google Patents

Novel spacer moiety for poly(ethylene glycol)-modified peptide-based co mpounds Download PDF

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Publication number
CA2525399A1
CA2525399A1 CA002525399A CA2525399A CA2525399A1 CA 2525399 A1 CA2525399 A1 CA 2525399A1 CA 002525399 A CA002525399 A CA 002525399A CA 2525399 A CA2525399 A CA 2525399A CA 2525399 A1 CA2525399 A1 CA 2525399A1
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CA
Canada
Prior art keywords
moiety
compound
peptide
poly
ethylene glycol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
CA002525399A
Other languages
French (fr)
Inventor
Christopher P. Holmes
David Tumelty
Qun Yin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Affymax Inc
Original Assignee
Affymax, Inc.
Christopher P. Holmes
David Tumelty
Qun Yin
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Affymax, Inc., Christopher P. Holmes, David Tumelty, Qun Yin filed Critical Affymax, Inc.
Publication of CA2525399A1 publication Critical patent/CA2525399A1/en
Abandoned legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/524—Thrombopoietin, i.e. C-MPL ligand
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/505—Erythropoietin [EPO]

Abstract

The present invention relates to a compound comprising a peptide moiety, a spacer moiety and a water-soluble polymer moiety such as a poly(ethylene glycol) moiety. The spacer moiety is between the peptide moiety and the water-soluble polymer moiety. The spacer moiety has the structure: -NH-(CH2).alpha.-[O-(CH2).beta.].gamma.-O.delta.-(CH2).epsilon.-Y~- wherein .alpha., .beta., .gamma., .delta.,and .epsilon. are each integers whose values are independently selected.

Claims (36)

1. A compound comprising a peptide moiety, a spacer moiety, and a water-soluble polymer moiety wherein the spacer moiety is between the peptide moiety and the water-soluble polymer moiety and having the structure:

-NH-(CH2).alpha.-[O-(CH2).beta.].gamma.-O.delta.-(CH2).epsilon.-Y-wherein .alpha., .beta., .gamma., .delta.,and .epsilon. are each integers whose values are independently selected.
2. The compound of claim 1, wherein .alpha. is an integer, 1 <= .alpha. <= 6;

.beta. is an integer, 1 <= .beta. <=6;

.epsilon. is an integer, 1 <= .epsilon.<= 6;

.delta.is 0 or 1;

.gamma. is an integer, 0 <= .gamma. <= 10; and Y is either NH or CO.
3. The compound of claim 2, wherein .gamma. > 1 and .beta. = 2.
4. The compound of claim 1 wherein .alpha.=.beta.=.epsilon.=2;

.gamma.=.delta.= 1; and Y is NH.
5. The compound of claim 1 wherein the water-soluble polymer moiety is a poly(ethylene glycol) moiety.
6. The compound of claim 5 wherein the molecular weight of the poly(ethylene glycol) moiety is more than 20 KDalton.
7. The compound of claim 5, wherein the poly(ethylene glycol) moiety is linear.
8. The compound of claim 5, wherein the poly(ethylene glycol) moiety has a molecular weight from 20 to 40 KDalton.
9. The compound of claim 5, wherein the poly(ethylene glycol) moiety has polydispersity value (M w/M n) of less than 1.20.
10. The compound of claim 1, wherein the peptide moiety is peptide monomer comprising a single peptide.
11. The compound of claim 1, wherein the peptide moiety is a peptide dimer comprising two peptides linked by a linker moiety.
12. The compound of claim 10 or 11, wherein each peptide comprises no more than 50 amino acid monomers.
13. The compound of claim 12, wherein each peptide comprises between about 10 and 25 amino acid monomers.
14. The compound of claim 1, wherein the peptide moiety comprises one or more peptides which bind to erythropoietin-receptors.
15. The compound of claim 1, wherein the peptide moiety comprises one or more peptides which bind to thrombopoietin-receptors.
16. A pharmaceutical composition comprising (a) a compound comprising a peptide moiety, a spacer moiety; and a water-soluble polymer moiety wherein the spacer moiety is between the peptide moiety and the water-soluble polymer moiety and having the structure -NH-(CH2).alpha. [O-(CH2).beta.].gamma. O.delta.-(CH2).epsilon. Y-wherein .alpha. .beta., .gamma., .delta.,and .epsilon. are each integers whose values are independently selected; and (b) one or more pharmaceutically acceptable diluents, preservatives, solubilizers, emulsifiers, adjuvants and/or carriers.
17. The composition of claim 16, wherein .alpha. is an integer, 1 <= .alpha. <= 6;

.beta. is an integer, 1 <=.beta. <= 6;

.epsilon. is an integer, 1 <= .epsilon. <= 6;

.delta.is 0 or 1;

.gamma. is an integer, 0 <= .gamma. <= 10; and Y is either NH or CO.
18. The composition of claim 17, wherein .gamma. > 1 and .beta. = 2.
19. The composition of claim 16 wherein .alpha.=.beta.=.epsilon.=2;

.gamma.=.delta.=l; and Y is NH.
20. The composition of claim 16 wherein the water-soluble polymer moiety is a poly(ethylene glycol) moiety.
21. The composition of claim 20 wherein the molecular weight of the poly(ethylene glycol) moiety is more than 20 KDalton.
22. The composition of claim 20, wherein the poly(ethylene glycol) moiety is linear.
23. The composition of claim 20, wherein the poly(ethylene glycol) moiety has a molecular weight from 20 to 40 KDalton.
24. The composition of claim 20, wherein the poly(ethylene glycol) moiety has polydispersity value (M w/M n) of less than 1.20.
25. The composition of claim 16, wherein the peptide moiety is peptide monomer comprising a single peptide.
26. The composition of claim 16, wherein the peptide moiety is a peptide dimer comprising two peptides linked by a linker moiety.
27. The composition of claim 25 or 26, wherein each peptide comprises no more than 50 amino acid monomers.
28. The composition of claim 27, wherein each peptide comprises between about 10 and 25 amino acid monomers.
29. The composition of claim 16, wherein the peptide moiety comprises one or more peptides which bind to erythropoietin-receptors.
30. The composition of claim 16, wherein the peptide moiety comprises one or more peptides which bind to thrombopoietin-receptors.
31. The compound of claim 1, wherein .alpha.=2;
.gamma.=.delta.=.beta.=.epsilon.=0; and Y is CO.
32. The composition of claim 16, wherein .alpha.=2;

.gamma.=.delta.=.beta.=.epsilon.=0; and Y is CO.
33. The compound of claim 5 wherein the poly(ethylene glycol) moiety comprises at least one monomeric poly(ethylene glycol) chain.
34. The compound of claim 33 wherein each poly(ethylene glycol) chain has a molecular weight from 20 to 40 KDaltons.
35. The composition of 16 wherein the poly(ethylene glycol) moiety comprises at least one monomeric poly(ethylene glycol) chain.
36. The compound of claim 35 wherein each poly(ethylene glycol) chain has a molecular weight from 20 to 40 KDaltons.
CA002525399A 2003-05-12 2004-05-12 Novel spacer moiety for poly(ethylene glycol)-modified peptide-based co mpounds Abandoned CA2525399A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US46999603P 2003-05-12 2003-05-12
US60/469,996 2003-05-12
PCT/US2004/014887 WO2004100997A2 (en) 2003-05-12 2004-05-12 Spacer moiety for poly(ethylene glycol) -modified peptides

Publications (1)

Publication Number Publication Date
CA2525399A1 true CA2525399A1 (en) 2004-11-25

Family

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Family Applications (1)

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CA002525399A Abandoned CA2525399A1 (en) 2003-05-12 2004-05-12 Novel spacer moiety for poly(ethylene glycol)-modified peptide-based co mpounds

Country Status (16)

Country Link
US (2) US7919118B2 (en)
EP (2) EP2204193A3 (en)
JP (2) JP2007500218A (en)
KR (1) KR101160611B1 (en)
CN (1) CN1849141A (en)
AU (1) AU2004238364A1 (en)
BR (1) BRPI0411166A (en)
CA (1) CA2525399A1 (en)
EA (1) EA010015B1 (en)
IL (1) IL171885A0 (en)
IS (1) IS8168A (en)
MX (1) MXPA05012314A (en)
NO (1) NO20055848L (en)
NZ (2) NZ543934A (en)
WO (1) WO2004100997A2 (en)
ZA (1) ZA200509970B (en)

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AU2004238364A1 (en) 2004-11-25
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US7919118B2 (en) 2011-04-05
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US20070032408A1 (en) 2007-02-08

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