Granted Patent
B2
US 12,629,407 · App. 15/556,996 · Granted May 19, 2026
Conjugates of an il-7 moiety and a polymer
Inventors:
Deborah H. Charych (Albany, CA); Ping Zhang (Millbrae, CA); Peter Benedict Kirk (San Mateo, CA)
Assignee:
Nektar Therapeutics
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Conjugates of an IL-7 moiety and one or more nonpeptidic, water-soluble polymers are provided. Typically, the non-peptidic, water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided, among other things, are compositions comprising conjugates, methods of making conjugates, and methods of administering compositions to an individual.
Claims (16)
1 . A conjugate comprising an interleukin-7 (IL-7) moiety covalently attached to a poly (ethylene glycol) polymer at an amino group of the IL-7 moiety via an amine linkage, the conjugate comprising a structure:
wherein:
each (n) is independently an integer having a value of from 2 to 4000;
IL-7 is an IL-7 moiety,
and wherein the conjugate possesses a measurable degree of IL-7 bioactivity.
2 . The conjugate of claim 1 , wherein for each structure, the poly (ethylene glycol) polymer has a weight-average molecular weight in a range of from about 500 Daltons to about 100,000 Daltons.
3 . The conjugate of claim 1 , wherein one, two, three or four poly (ethylene glycol) polymers are attached to the IL-7 moiety.
4 . The conjugate of claim 3 , wherein one, two or three poly (ethylene glycol) polymers are attached to the IL-7 moiety.
5 . The conjugate of claim 4 , wherein one or two poly (ethylene glycol) polymers are attached to the IL-7 moiety.
6 . The conjugate of claim 5 , wherein one poly (ethylene glycol) polymer is attached to the IL-7 moiety.
7 . The conjugate of claim 1 , wherein the IL-7 moiety has an amino acid sequence selected from the group consisting of SEQ ID NO: 1; SEQ ID NO: 2; SEQ ID NO: 3; SEQ ID NO: 4; SEQ ID NO: 5; SEQ ID NO: 6; SEQ ID NO: 7; and SEQ ID NO: 8.
8 . A pharmaceutical composition comprising the conjugate of claim 1 and a pharmaceutically acceptable excipient.
9 . The conjugate of claim 1 , wherein the weight average molecular weight of the poly (ethylene glycol) polymer comprised in the conjugate is from about 20,000 Daltons to about 85,000 Daltons.
10 . The conjugate of claim 1 ,
wherein the weight average molecular weight of the poly (ethylene glycol) polymer is about 20,000 Daltons or about 40,000 Daltons.
11 . The conjugate of claim 1 , wherein the poly (ethylene glycol) polymer is covalently attached to an amino group at the N-terminus of the IL-7 moiety.
Assignments (3)
RELEASE OF SECURITY INTEREST
Recorded Apr 17, 2020
From: TC LENDING, LLC, AS COLLATERAL AGENT
To: NEKTAR THERAPEUTICS
Reel/Frame 053180/0009 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 23, 2018
From: CHARYCH, DEBORAH H.; ZHANG, PING; KIRK, PETER BENEDICT
To: NEKTAR THERAPEUTICS
Reel/Frame 045326/0805 →
SECURITY INTEREST
Recorded Sep 28, 2017
From: NEKTAR THERAPEUTICS
To: TC LENDING, LLC, AS COLLATERAL AGENT
Reel/Frame 043725/0726 →
Continuity (2)
Provisional Application
62131634
· Mar 11, 2015
References Cited (91)
US 5739208A
· Harris
· 1998
[cited by applicant]
US 5932462A
· Harris et al.
· 1999
[cited by applicant]
US 6177079B1
· Grabstein et al.
· 2001
[cited by applicant]
US 7589179B2
· Gillies et al.
· 2009
[cited by applicant]
US 7956032B2
· Defrees et al.
· 2011
[cited by applicant]
US 20040136952A1
· Bhaskaran et al.
· 2004
[cited by applicant]
US 20050014903A1
· Kozlowski et al.
· 2005
[cited by applicant]
US 20050249701A1
· Morre
· 2005
[cited by examiner]
US 20060141581A1
· Gillies et al.
· 2006
[cited by applicant]
CN 102145178B
· 2012
[cited by examiner]
WO WO9012874A2
· 1990
[cited by applicant]
WO WO9945964A1
· 1999
[cited by applicant]
WO WO0162827A2
· 2001
[cited by applicant]
WO WO02085300A2
· 2002
[cited by applicant]
WO WO03044056A2
· 2003
[cited by applicant]
WO WO2004060300A2
· 2004
[cited by applicant]
WO WO2008106186A2
· 2008
[cited by applicant]
WO WO2012065086A1
· 2012
[cited by examiner]
WO WO2013020079A2
· 2013
[cited by applicant]
Eliason, J.F., Pegylated Cytokines—Potential Application in Immunotherapy of Cancer. BioDrugs. 2001; 15(11):705-11.
[cited by examiner]
Bansal et al., PEGylation improves pharmacokinetic profile, liver uptake and efficacy of Interferon gamma in liver fibrosis. J Control Release. Sep. 25, 2011;154(3):233-40.
[cited by examiner]
Mattos et al., PEGylation of interleukin-10 improves the pharmacokinetic profile and enhances the antifibrotic effectivity in CCI4-induced fibrogenesis in mice. J Control Release. Aug. 20, 2012;162(1):84-91.
[cited by examiner]
Cheng et al. Analytical Measurement of PEGylated Molecules. Bioconjug Chem. May 16, 2012;23(5):881-99.
[cited by examiner]
J. Kling, PEGylation of Biologics. Bioprocess International, Mar. 1, 2013.
[cited by examiner]
Fischer et al., “Recombinant human acetylcholinesterase expressed in
[cited by applicant]
Fry et al., “Interleukin-7 restores immunity in athymic T-cell-depleted hosts”, Blood, vol. 97, pp. 1525-1533, (2001).
[cited by applicant]
Ghazawi et al., “IL-7 downregulates IL-7Rα expression in human CD8 T cells by two independent mechanisms”, Immunology and Cell Biology, vol. 91, pp. 149-158, (2013).
[cited by applicant]
Heldt et al., “The Use of Glycidol to Introduce Aldehyde Functions Into Proteins-Application to the Fluorescent Labelling of Bovine Serum Albumin and Avidin”, Eur. J. Org. Chem., pp. 5429-5433, (2007).
[cited by applicant]
Komschiles et al., “Diverse immunological and hematological effects of interleukin 7: implications for clinical application”, Journal of Leukocyte Biology, vol. 58, pp. 623-633, (Dec. 1995).
[cited by applicant]
Kroemer et al., “Comparison of the 3D models fo four different human IL-7 isoforms with human and murine IL-7”, Protein Engineering, vol. 11, No. 1, pp. 31-40, (1998).
[cited by applicant]
Kroemer et al., “Homology modeling study of the human interleukin-7 receptor complex”, Protein Engineering, vol. 9, No. 12, pp. 1135-1142, (1996).
[cited by applicant]
Kronman et al., “Production and secretion of high levels of recombinant human acetylcholinesterase in cultured cell lines: microheterogeneity of the catalytic subunit”, Gene, vol. 121, pp. 295-304, (1992).
[cited by applicant]
Li et al., “Recombinant IL-7 enhances the potency of GM-CSF-secreting tumor cell immunotherapy”, Clinical Immunology, vol. 123, pp. 155-165, (2007).
[cited by applicant]
Luchansky et al., “Metabolic Functionalization of Recombinant Glycoproteins”, Biochemistry, vol. 43, pp. 12358-12366, (2004).
[cited by applicant]
Mackall et al., “IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation”, Blood, vol. 97, pp. 1491-1497, (2001).
[cited by applicant]
Markley et al., “IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice”, Blood, vol. 115, No. 17, pp. 3508-3519, (2010).
[cited by applicant]
Mor et al., “Expression of Recombinant Human Acetylcholinesterase in Transgenic Tomato Plants”, Biotechnol. Bioeng., vol. 75, pp. 259-266, (2001).
[cited by applicant]
Morel et al., “Expression and processing of vertebrate acetylcholinesterase in the yeast
[cited by applicant]
Morrissey et al., “Administration of IL-7 to Mice with Cyclophosphamide-Induced Lymphopenia Accelerates Lymphocyte Repopulation”, The Journal Of Immunology, vol. 146, No. 5, pp. 1547-1552, (Mar. 1, 1991).
[cited by applicant]
Nam et al., “Marked enhancement of antigen-specific T-cell responses by IL-7-fused nonlytic, but not lytic, Fc as a genetic adjuvant”, Eur. J. Immunol., vol. 40, pp. 351-358, (2010).
[cited by applicant]
Namen et al., “B Cell Precursor Growth-Promoting Activity”, J. Exp. Med., vol. 167, pp. 988-1002, (Mar. 1988).
[cited by applicant]
Ouchi et al., “Design of Antitumor Agent-Terminated Poly(Ethylene Glycol) Conjugate as Macromolecular Prodrug”, Polymer Preprints, vol. 38, No. 1, pp. 582-583, (1997).
[cited by applicant]
Ouellette et al., “Production and purification of refolded recombinant human IL-7 from inclusion bodies”, Protein Expression and Purification, vol. 30, pp. 156-166, (2003).
[cited by applicant]
Sims et al., “A Method for the Estimation of Polyethylene Glycol in Plasma Protein Fractions”, Analytical Biochemistry, vol. 107, pp. 60-63, (1980).
[cited by applicant]
Storek et al., “Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys”, Blood, vol. 101, pp. 4209-4218, (2003).
[cited by applicant]
Tang et al., “IL-7 inhibits tumor growth by promoting T cell-mediated antitumor immunity in Meth A model”, Immunology Letters, vol. 158, pp. 159-166, (2014).
[cited by applicant]
Vudattu et al., “Expression analysis and functional activity of interleukin-7 splice variants”, Genes and Immunity, vol. 10, pp. 132-140, (2009).
[cited by applicant]
Wong et al., “The IL-15-based superagonist ALT-803 promotes the antigen-independent conversion of memory CD8
[cited by applicant]
Zalipsky, “Chemistry of polyethylene glycol conjugates with biologically active molecules”, Advanced Drug Delivery Reviews, vol. 16, pp. 157-182, (1995).
[cited by applicant]
Zalipsky et al., “Use of Functionalized Poly(Ethylene Glycol)s for Modification of Polypeptides”, Poly(Ethylene Glycol) Chemistry: Biotechnical and Biomedical Applications, edited by J. Milton Harris, Plenum Press, New …
[cited by applicant]
Zustiak et al., “Hydrolytically Degradable Poly(Ethylene Glycol) Hydrogel Scaffolds with Tunable Degradation and Mechanical Properties”, Biomacromolecules, vol. 11, pp. 1348-1457, (2010).
[cited by applicant]
PCT International Search Report and the Written Opinion corresponding to PCT Application No. PCT/US2016/022146 date of mailing Jul. 18, 2016.
[cited by applicant]
PCT International Preliminary Report on Patentability corresponding to PCT Application No. PCT/US2016/022146 date of mailing Sep. 21, 2017.
[cited by applicant]
Enzon Pharmaceuticals, Macromolecular Engineering Technologies, 16 pages, (2004).
[cited by applicant]
Nektar™—Transforming Therapeutics, Nektar Molecule Engineering: Polyethylene Glycol and Derivatives for Advanced PEGylation, 24 pages, Catalog—2003, (Jul. 2003).
[cited by applicant]
Nektar™—Transforming Therapeutics, Nektar Advanced PEGylation: Polyethylene Glycol and Derivatives for Advanced PEGylation, 27 pages, Catalog—2004, (Jul. 2004).
[cited by applicant]
Nektar™—Transforming Therapeutics, Nektar Advanced PEGylation: Polyethylene Glycol and Derivatives for Advanced PEGylation, 33 pages, (Catalog 2005-2006).
[cited by applicant]
NOF Corporation, PEG Derivatives, Phospholipid and Drug Delivery Materials for Pharmaceuticals, 46 pages, Catalogue 2003—1
[cited by applicant]
NOF Corporation, PEG Derivatives, Phospholipid and Drug Delivery Materials for Pharmaceuticals, 27 pages, Catalogue 2003—2
[cited by applicant]
NOF Corporation, PEG Derivatives, Phospholipids and Drug Delivery Materials for Pharmaceutical Products and Formulations, 60 pages, Catalogue Ver. 8, (Apr. 2006).
[cited by applicant]
Polypure Products, PEG amines; PEG acids and amino acids; PEG thiols and disulfides; Biotins, 5 pages, (Apr. 2004).
[cited by applicant]
Polypure Products, PEG amines; PEG acids and amino acids; PEG thiols and disulfides; Biotins, 5 pages, (Apr. 2005).
[cited by applicant]
Quanta Biodesign, Labeling, Derivatization and Crosslinking Reagents for Biological and Related Materials with dPEG™, 38 pages, (Mar. 12, 2004).
[cited by applicant]
Quanta Biodesign, Labeling, Modification and Crosslinking Reagents incorporating our unique monodispersed dPEG™ Technology, 31 pages, (Nov. 5, 2004).
[cited by applicant]
Quanta Biodesign, Ltd., Leading innovator, producer and provider of monodisperse discrete PEG™ (dPEG™) derivatives, (Product Catalog), 26 pages, (Updated: Jul. 18, 2005).
[cited by applicant]
Quanta Biodesign, Ltd., Leading innovator, producer and provider of monodisperse discrete PEG™ (dPEG™) derivatives, (Product Catalog), 26 pages, (Updated: Nov. 17, 2005).
[cited by applicant]
Shearwater Polymers, Inc., Polyethylene Glycol Derivatives, 50 pages, Catalog—(Mar. 1995).
[cited by applicant]
Shearwater Polymers, Inc., Polyethylene Glycol Derivatives, 55 pages, Catalog 1997-1998, (Jul. 1997).
[cited by applicant]
Shearwater Polymers, Inc., Polyethylene Glycol and Derivatives: Functionalized Biocompatible Polymers for Research and Pharmaceuticals, 50 pages, Catalog—(Jan. 2000).
[cited by applicant]
Shearwater Corporation, Polyethylene Glycol and Derivatives for Biomedical Applications, 20 pages, Catalog—(Jul. 2001).
[cited by applicant]
Australian First Examination Report corresponding to Australian Patent Application No. 2016228555 date of report Dec. 14, 2020.
[cited by applicant]
English Translation of the Notification of the First Office Action corresponding to Chinese Patent Application No. 20168001816.7 date of notification Sep. 2, 2020.
[cited by applicant]
English Translation of the Notice of Final Rejection corresponding to Japanese Patent Application No. 2017-547157 mailing date Oct. 30, 2020.
[cited by applicant]
English Translation of the 1
[cited by applicant]
European Communication corresponding to European Patent Application No. 16762659.7 dated Jul. 6, 2018.
[cited by applicant]
European Communication corresponding to European Patent Application No. 16762659.7 dated Jun. 25, 2019.
[cited by applicant]
European Communication corresponding to European Patent Application No. 16762659.7 dated Jun. 16, 2020.
[cited by applicant]
English Translation of Israel Examination Report corresponding to Israel Patent Application No. 201747031687 dated Jan. 30, 2020.
[cited by applicant]
English Translation of Japanese Notice of Reasons for Rejection corresponding to Japanese Patent Application No. 2017-547157 mailing date Dec. 26, 2019.
[cited by applicant]
English Translation of Chinese Notification of Second Office Action corresponding to Chinese Patent Application No. 201680014816.7 date of notification Jun. 11, 2021.
[cited by applicant]
English Translation of Indian Examination Report corresponding to Indian Patent Application No. 201747031687 date of dispatch Jan. 30, 2020.
[cited by applicant]
English Translation of 2
[cited by applicant]
Katzman et al., “Opposing functions of IL-2 and IL-7 in the regulation of immune responses”, Cytokine, Vo. 56, pp. 116-121, (2011).
[cited by applicant]
Verhoef et al., “Questioning the Use of PEGylation for Drug Delivery”, Drug Deliv. Transl. Rev., vol. 3, No. 6, pp. 499-503, (Dec. 2013).
[cited by applicant]
Canadian Office Action corresponding to Canadian Patent Application No. 2,978,330 dated Jun. 9, 2022.
[cited by applicant]
Canadian Office Action corresponding to Canadian Patent Application No. 2,978,330 dated Feb. 10, 2023.
[cited by applicant]
English Translation of Chinese Rejection Decision corresponding to Chinese Patent Application No. 201680014816.7 date of notification Jan. 20, 2022.
[cited by applicant]
European Communication corresponding to European Patent Application No. 16 762 659.7 dated Mar. 14, 2022.
[cited by applicant]
English Translation of Japanese Notice of Reasons for Rejection corresponding to Japanese Patent Application No. 2022-129624 mailing date Jul. 24, 2023.
[cited by applicant]