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WO2013038392A1 - Peptides capables de se lier aux cellules leucémiques b, conjugués, et compositions les contenant et leurs utilisations - Google Patents

Peptides capables de se lier aux cellules leucémiques b, conjugués, et compositions les contenant et leurs utilisations Download PDF

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Publication number
WO2013038392A1
WO2013038392A1 PCT/IB2012/054865 IB2012054865W WO2013038392A1 WO 2013038392 A1 WO2013038392 A1 WO 2013038392A1 IB 2012054865 W IB2012054865 W IB 2012054865W WO 2013038392 A1 WO2013038392 A1 WO 2013038392A1
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WO
WIPO (PCT)
Prior art keywords
agent
peptide
composition
seq
cell
Prior art date
Application number
PCT/IB2012/054865
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English (en)
Inventor
Michael Firer
Original Assignee
Ariel-University Research And Development Company, Ltd.
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 Ariel-University Research And Development Company, Ltd. filed Critical Ariel-University Research And Development Company, Ltd.
Publication of WO2013038392A1 publication Critical patent/WO2013038392A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0002—General or multifunctional contrast agents, e.g. chelated agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present application incorporates-by-reference nucleotide and/or amino acid sequences which are present in the file named "20120905_121-72-PCT_SequenceListing ST25.txt", which is 5 kilobytes in size, and which was created on 5 September 2012 in the IBM-PC machine format, having an operating system compatibility with MS-Windows, and is submitted herewith.
  • the invention in some embodiments, relates to the field of chemistry and pharmacology, and more specifically, but not exclusively, to a B-cell targeting peptide useful for selective targeting to B-cell leukemic cells.
  • the invention in some embodiments, relates to the field of cancer treatment, and more specifically, but not exclusively, to compositions comprising a peptide, and their use in the treatment and diagnosis of cancers such as B-cell leukemias.
  • provided herein is a method of selectively directing an agent to a B- cell leukemic cell in a subject by administering to the subject a composition comprising the agent and peptide that targets a B-cell leukemia cell.
  • Cancer is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Cancer cells can spread to other parts of the body (metastasis) through the blood and lymph systems.
  • Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow and is characterized by an abnormal proliferation of blood cells, usually leukocytes. Leukemia is divided into four categories: myelogenous (myeloid) or lymphocytic (lymphoid), each of which can be acute or chronic.
  • myelogenous myeloid
  • lymphocytic lymphocytic
  • chemotherapeutic agents lack cancer cell specificity, causing a wide range of adverse side-effects, including nausea, vomiting, anemia, and hair loss, their use limited due to concentration-dependent toxicity in normal cells. Furthermore, multiple drug resistance is frequently induced in cancer cells upon repeated exposure to chemotherapeutic agents. The therapeutic index of chemotherapeutic agents may be greatly improved if they could specifically target cancer cells and tissue.
  • compositions including B-cell leukemia targeting peptides and methods of using the targeting peptides in detecting, diagnosing, treating and monitoring treatment of cancer or cancer cells in vivo and in vitro are useful for, inter alia, selectively delivering therapeutic and or diagnostic agents to B-cell leukemic cells.
  • the peptide is a component in a composition whereby, for example, the agent is coupled to the peptide; the agent is complexed with the peptide and a carrier, or a peptide-decorated carrier encapsulates the agent.
  • aspects of some embodiments of the invention relate to a peptide or a peptidomimetic thereof configured for selective binding to B-cell leukemic cells, in some embodiments allowing the peptide to act as a B-cell Leukemia targeting ligand.
  • the target cancer cell selectively internalizes the peptide.
  • the target cancer cell selectively internalizes a composition comprising the peptide.
  • aspects of some embodiments of the invention relate to methods and compositions for the treatment and diagnosis or detection of cancer, such as B-cell leukemia, using targeted agent delivery by a composition comprising a peptide including for example peptide-agent conjugates, where the peptide moiety is configured for selective binding to, and in some embodiments, internalization by, B-cell leukemic cells.
  • a peptide wherein the peptide comprises a subsequence of at least 5 consecutive amino acids selected from the sequence Thr-Ala-Thr-Ala-Ser-Gln-Ser (SEQ ID NO:l)
  • the peptide is a heptapeptide comprising the sequence Thr- Ala-Thr-Ala-Ser-Gln-Ser (SEQ ID NO:l). In some embodiments, the peptide is a hexapeptide comprising a sequence selected from the group consisting of Thr-Ala-Thr-Ala-Ser-Gln (SEQ ID NO:2) and Ala-Thr-Ala-Ser- Gln-Ser (SEQ ID NO:3).
  • a peptide or peptidomimetic containing the amino acid sequence set forth in any one of SEQ ID NO: 1-6, or a conservative substitute or peptidomimetic of one of these sequences.
  • a cyclic peptide or peptidomimetic comprising SEQ ID NO: l .
  • the cyclic peptide is 7, 8, 9, 10, 11, 12, 13, 14, 15, or up to 35 amino acid residues long.
  • the peptide according to SEQ ID NO: l is synthesized with terminal cysteine residues and cyclic by oxidation.
  • a cyclic peptide or peptidomimetic comprising SEQ ID NO: 16.
  • the cyclic peptide is 7, 8, 9, 10, 11, 12, 13, 14, 15, or up to 35 amino acid residues long.
  • the peptide comprising SEQ ID NO: 16 is synthesized with terminal cysteine residues and cyclicized by oxidation.
  • a cyclic peptide or peptidomimetic comprising SEQ ID NO: 17.
  • the cyclic peptide is 7, 8, 9, 10, 11, 12, 13, 14, 15, or up to 35 amino acid residues long.
  • the peptide according to SEQ ID NO: 17 is synthesized with terminal cysteine residues and cyclicized by oxidation.
  • a cyclic peptide or peptidomimetic comprising SEQ ID NO: 18.
  • the cyclic peptide is 7, 8, 9, 10, 11, 12, 13, 14, 15, or up to 35 amino acid residues long.
  • the peptide according to SEQ ID NO: 18 is synthesized with terminal cysteine residues and cyclicized by oxidation. According to an aspect of some embodiments of the invention there is also provided a peptide which includes one or two amino acid substitutions.
  • the peptide comprises at least 6 consecutive amino acids selected from the group of at least 7 amino acid residues.
  • composition further comprises an agent, for example a therapeutic agent or a diagnostic agent.
  • agent for example a therapeutic agent or a diagnostic agent.
  • the peptide is directly linked to the agent.
  • the peptide is linked to the agent via a linker.
  • the agent is selected from an active agent and a diagnostic agent.
  • the agent comprises an active agent.
  • the active agent is selected from the group consisting of a toxin, an antibody, an antigen, a biological material, a chemical material, a drug, an enzyme, a hormone, a nucleic acid, a peptide, a protein, and a radioisotope.
  • the agent comprises a diagnostic agent, such as a probe or a tracer.
  • the diagnostic agent includes, but is not limited to, fluorescent, metallic, enzymatic and radioactive markers such as biotin, gold, ferritin, alkaline phosphatase, ⁇ -galactosidase, peroxidase, urease, fluorescein or derivative thereof, rhodamine or derivative thereof, tritium, 14 C , iodination, a luminescent label, a PET-active substance or a SPECT-active substance.
  • fluorescent, metallic, enzymatic and radioactive markers such as biotin, gold, ferritin, alkaline phosphatase, ⁇ -galactosidase, peroxidase, urease, fluorescein or derivative thereof, rhodamine or derivative thereof, tritium, 14 C , iodination, a luminescent label, a PET-active substance or a SPECT-active substance.
  • the carrier is a pharmaceutically acceptable carrier.
  • Such carriers are well known in the art and include, for example, aqueous solutions such as water or physiologically buffered saline or other solvents or vehicles such as glycols, glycerol, oils such as olive oil or injectable organic esters.
  • the carrier is a macromolecular structure such as a micelle, a liposome a microcarrier a nanocarrier or a dendrimer
  • the use of a composition comprising the peptide according to the teachings herein, for detection of the presence of cancer cells in a patient following cancer therapy.
  • the peptide comprises a sequence set forth in any one of SEQ ID NOS: l-6.
  • the peptide comprises a sequence set forth in SEQ ID NO: l .
  • the peptide comprises a sequence set forth in any one of SEQ ID NOS: 16-18.
  • the peptide is covalently linked to a diagnostic agent.
  • the peptide is non-covalently bound to a diagnostic agent.
  • the peptide is a cyclic peptide.
  • the composition comprises the peptide according to the teachings herein, in a pharmaceutically acceptable carrier.
  • the composition is useful in the treatment and/or diagnosis and/or detection of cancer, in some embodiments B-cell leukemia.
  • the peptide comprises a sequence set forth in any one of SEQ ID NOS: l-6.
  • the peptide comprises a sequence set forth in SEQ ID NO: l .
  • the peptide comprises a sequence set forth in any one of SEQ ID NOS: 16-18.
  • the peptide is covalently linked to a therapeutic or diagnostic agent.
  • the peptide is non-covalently bound to a therapeutic or diagnostic agent.
  • the peptide is a cyclic peptide.
  • the carrier comprises a dendrimer, a micelle, a liposome or a nanoparticle.
  • a method of detecting presence of a B-cell leukemic cell in a subject comprising
  • composition comprising a peptide conjugated to a diagnostic agent, wherein the peptide comprises up to 35 amino acids in length and an amino acid sequence selected from any one of SEQ ID NOS: l-6, and wherein the polypeptide is capable of binding to a B-cell leukemia cell;
  • an increase in binding of the peptide conjugated to a diagnostic agent as compared to a negative control indicates the presence of a B-leukemic tumor cell in the tissue sample.
  • the contacting is performed ex vivo. In some embodiments, the contacting is performed in vitro. As is clear to a person having ordinary skill in the art, such embodiments do not require the presence of the subject during the contacting.
  • the tissue sample is a blood sample or a bone marrow sample.
  • a method of detecting the presence or absence of a B-cell leukemic cell in a subject comprising:
  • an increase in binding of the polypeptide conjugated to a detectable molecule as compared to a negative control indicates the presence of a tumor cell in the subject.
  • the peptide comprises SEQ ID NO: l or a peptidomimetic thereof. In some embodiments the peptide is a cyclic peptide or peptidomimetic thereof.
  • the diagnostic agent comprises fluorescent, metallic, enzymatic and radioactive markers such as biotin, gold, ferritin, alkaline phosphatase, ⁇ -galactosidase, peroxidase, urease, fluorescein or derivative thereof, rhodamine or derivative thereof, tritium, 14 C , iodination, a luminescent label, a PET-active substance or a SPECT-active substance.
  • kits for detecting presence or absence of a tumor cell in a subject including a composition comprising a peptide conjugated to a detectable molecule to a subject, wherein the peptide comprises up to 35 amino acids in length and an amino acid sequence selected from any one of SEQ ID NO: 1-6, and wherein the peptide is capable of binding to a B-cell leukemia cell.
  • the peptide comprises SEQ ID NO: l .
  • the peptide comprises a sequence set forth in any one of SEQ ID NOS:16-18.
  • the peptide is a cyclic peptide or peptidomimetic thereof.
  • the peptide is selected according to its ability to bind with a high degree of specificity to unique, complementary receptors expressed on the surface of specific populations of target cells, particularly B-cells. In some embodiments, the peptide is selectively internalized by the target cancer cell.
  • the peptide-agent conjugate is constructed to specifically target such cells where the peptide part constitutes a cell-targeting part of the conjugate.
  • An agent can be any natural or non-natural material including a biological material, such as a cell or phage; an organic chemical, such as a small molecule; a radionuclide; a nucleotide or oligonucleotide; a polypeptide; or a peptide or peptidomimetic.
  • agents useful for implementing the teachings herein, for example in diagnostic and therapeutic methods include, without limitation, therapeutic agents; cancer chemotherapeutic agents, cytotoxic agents, pro-apoptotic agents, anti-lymphangiogenic agents, detectable labels and imaging agents; and tags or other insoluble supports.
  • the agent comprises, for example, a toxin, an antibody, an antigen, a biological material, a chemical material, a drug, an enzyme, a hormone, a nucleic acid, a peptide, a protein.
  • the agent comprises a macromolecular structure such as, for example, a micelle or a liposome.
  • the active agent comprises a chemotherapeutic agent, such that the conjugate comprises, for example, the peptide as a cell-targeting portion and the chemotherapeutic agent as an apoptosis-inducing portion.
  • the chemotherapeutic agent comprises a toxin, such as a plant toxin or a bacterial toxin.
  • the agent is a diagnostic agent.
  • the diagnostic agent is a probe or a tracer.
  • the diagnostic agent is a detectable agent, such as a fluorescent agent (e.g., fluorescein), an enzyme or a radioactive agent (e.g., includes a radioisotope).
  • the diagnostic agent is a chemical or biological signaling agent.
  • the fluorescent molecule FITC is conjugated to a peptide specific for a selected target antibody.
  • the peptide- FITC conjugate is added to a mixture of antibodies, including the target antibody, preferably in an assay format similar to the common Fluorescent Immunoassay test. The conjugate binds only to the target antibody, and this reaction can be used to measure the amount of target antibody in the mixture.
  • the conjugate be purified by any method known in the art, such as, for example, high performance liquid chromatography, ion exchange chromatography, gel electrophoresis, affinity chromatography and the like.
  • Some embodiments of the teachings herein provide peptides exhibiting selective binding to B-cell leukemic cells.
  • selective binding means that the peptides disclosed herein bind to the target cells with greater affinity than they binds to normal mammalian cells under specified conditions.
  • the peptides of the teachings herein bind the target B-cell leukemic cells with an affinity greater by at least one order of magnitude than their binding affinity to other mammalian cells under specified conditions.
  • the peptide is cyclic, for example, by synthesizing a peptide with two cysteine residues (e.g, at the C and N termini) and forming a cyclicizing disulfide bond, through the cysteine side chains.
  • a first amino acid having an uncharged side chain i.e., serine, threonine and glutamine
  • a second amino acid such as serine (Ser), threonine (Thr), asparagine (Asn) and glutamine (Gin), or an analog thereof.
  • the medicament comprises a peptide set forth in any one of SEQ ID NOS: l-6 and a therapeutic agent.
  • the peptide is coupled to the agent per se or via a linker.
  • the medicament comprises a peptide set forth in any one of SEQ ID NOS: l-6 and a dendrimer, and further comprises a therapeutic agent
  • the cancer is B-cell leukemia.
  • compositions may be in powder form for constitution with a suitable vehicle, e. g., sterile pyrogen- free water, before use.
  • a suitable vehicle e. g., sterile pyrogen- free water
  • penetrants appropriate to the barrier to be permeated are used in the formulation.
  • penetrants are generally known in the art.
  • lactose sucrose, mannitol and sorbitol
  • cellulose preparations such as maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP); granulating agents; and binding agents.
  • disintegrating agents may be added, such as the cross-linked polyvinylpyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.
  • compositions comprising a peptide and/or conjugate according to the teachings herein may take the form of tablets, lozenges, etc. formulated in conventional manner.
  • the peptides and/or conjugates may also be formulated in rectal or vaginal compositions such as suppositories or retention enemas, e. g., containing conventional suppository bases such as cocoa butter or other glycerides.
  • the conjugates according to the teachings herein, especially the peptide part, may include charged side chains or termini, and may be included in any of the above-described formulations as the free acids or bases, as esters or as pharmaceutically acceptable salts.
  • Pharmaceutically acceptable salts are those salts which substantially retain the biologic activity of the free acid or base and which are prepared, for example by reaction with inorganic acids. Pharmaceutical salts tend to be more soluble in aqueous and other protic solvents than are the corresponding free forms.
  • the peptide-decorated carrier is able to carry a therapeutic or diagnostic agent to a target cell, i.e. a B-cell leukemic cell.
  • the peptide is adsorbed onto a surface.
  • the surface is of a carrier particle (for example, a nanoparticle) made with either an inorganic or organic core.
  • nanoparticles include, but are not limited to, nanocrystalline particles, nanoparticles made by the polymerization of organic chains, activated carbon particles and protein-ceramic nanoplates.
  • Solid biodegradable microcarriers may be manufactured from biodegradable polymers including, but not limited to: biodegradable polyesters, such as poly(lactic acid), poly(glycolic acid), and copolymers (including block copolymers) thereof, as well as block copolymers of poly(lactic acid), poly(ethylene glycol), and poly (lactic-co-glycolic acid).
  • biodegradable polyesters such as poly(lactic acid), poly(glycolic acid), and copolymers (including block copolymers) thereof, as well as block copolymers of poly(lactic acid), poly(ethylene glycol), and poly (lactic-co-glycolic acid).
  • the agents disclosed herein are, for example, therapeutic agents or diagnostic agents.
  • the therapeutic agent is an enzyme selected from the group consisting of RNAase, DNAase, malate dehydrogenase, staphylococcal nuclease, delta- V-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6- phosphate dehydrogenase, glucoamylase and acetylcholinesterase.
  • peptides, peptide conjugates and compositions comprising the peptide according to the teachings herein will generally be used in an amount effective to achieve the intended purpose.
  • a composition comprising the peptide according to the teachings herein, is administered or applied in a therapeutically effective amount.
  • a therapeutically effective amount is an amount effective to ameliorate or prevent the symptoms, or prolong the survival of, the patient being treated. Determination of a therapeutically effective amount is well within the capabilities of those skilled in the art, especially in light of the detailed disclosure provided herein.
  • composition according to the teachings herein for the diagnosis of cancer.
  • the negative effect of drug conjugated to targeting peptide on the homeostasis of leukemic cells is shown to be significantly greater than the effect of either free drug or medium alone.
  • Aliquots of cell suspensions from leukemic and normal subjects are each added to 2 sets of microculture plates.
  • a composition comprising the peptide conjugate is added; to a second set of plates carrier is added alone.
  • Chronic Lymphocytic Leukemia and control mice (mice not inoculated with leukemic cells) are treated i.v. with the pharmaceutical composition comprising a peptide disclosed herein and a therapeutic agent using a previously defined protocol (for example, one or more times a week for several weeks, depending on the specific experimental conditions used) and animals are then assessed for the presence of CLL cells and other overt signs of disease.
  • a significant reduction in tumor burden and other signs of disease, as well as increased survival rate, is seen in mice treated with the pharmaceutical composition.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Toxicology (AREA)
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  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne des peptides se liant sélectivement aux cellules leucémiques B, des compositions contenant les peptides et des méthodes pour les utiliser afin de traiter et/ou de diagnostiquer une leucémie à lymphocytes B.
PCT/IB2012/054865 2011-09-18 2012-09-16 Peptides capables de se lier aux cellules leucémiques b, conjugués, et compositions les contenant et leurs utilisations WO2013038392A1 (fr)

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US201161535998P 2011-09-18 2011-09-18
US61/535,998 2011-09-18

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WO2013038392A1 true WO2013038392A1 (fr) 2013-03-21

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003014325A2 (fr) * 2001-08-10 2003-02-20 Xencor Automatisation de la conception des proteines pour l'elaboration de bibliotheques de proteines
WO2006010070A2 (fr) * 2004-07-10 2006-01-26 Board Of Regents, The University Of Texas System Compositions et procedes lies a des peptides se liant de facon selective avec des cellules de la leucemie
US7868142B2 (en) * 2006-10-13 2011-01-11 Canon Kabushiki Kaisha Protein, method for immobilizing protein, structure, biosensor, nucleic acid, vector and kit for detecting target substance

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003014325A2 (fr) * 2001-08-10 2003-02-20 Xencor Automatisation de la conception des proteines pour l'elaboration de bibliotheques de proteines
WO2006010070A2 (fr) * 2004-07-10 2006-01-26 Board Of Regents, The University Of Texas System Compositions et procedes lies a des peptides se liant de facon selective avec des cellules de la leucemie
US7868142B2 (en) * 2006-10-13 2011-01-11 Canon Kabushiki Kaisha Protein, method for immobilizing protein, structure, biosensor, nucleic acid, vector and kit for detecting target substance

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BUHL L ET AL.: "Surface immunoglobulin on B lymphocytes as a potential target for specific peptide ligands in chronic lymphocytic leukaemia", BR J HAEMATOL., vol. 116, no. 3, 30 March 2002 (2002-03-30), pages 549 - 554 *
DATABASE PROTEIN 21 March 2010 (2010-03-21), "hypothetical protein pK2044_00825 [Klebsiella pneumoniae NTUH-K2044]", accession no. P_001687993.1 *
DATABASE PROTEIN 4 December 2008 (2008-12-04), "hypothetical protein PC405168.00.0 [Plasmodium chabaudi chabaudi]", accession no. AH88669.1 *
JAGER S. ET AL.: "Leukemia-targeting ligands isolated from phage-display peptide libraries", LEUKEMIA, vol. 21, 2007, pages 411 - 420 *
TAKAHASHI S. ET AL.: "Selection of chronic lymphocytic leukemia binding peptides", CANCER RES, vol. 63, no. 17, 1 September 2003 (2003-09-01), pages 5213 - 5217 *

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