WO2015191969A1 - Treating lymphomas - Google Patents

Treating lymphomas Download PDF

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Publication number
WO2015191969A1
WO2015191969A1 PCT/US2015/035505 US2015035505W WO2015191969A1 WO 2015191969 A1 WO2015191969 A1 WO 2015191969A1 US 2015035505 W US2015035505 W US 2015035505W WO 2015191969 A1 WO2015191969 A1 WO 2015191969A1
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WO
WIPO (PCT)
Prior art keywords
μιη
composition
complexes
percent
lymphoma
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.)
Ceased
Application number
PCT/US2015/035505
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English (en)
French (fr)
Inventor
Svetomir N. Markovic
Wendy K. NEVALA
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.)
Mayo Foundation for Medical Education and Research
Mayo Clinic in Florida
Original Assignee
Mayo Foundation for Medical Education and Research
Mayo Clinic in Florida
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
Priority to MX2016016369A priority Critical patent/MX380597B/es
Priority to KR1020167035171A priority patent/KR102450563B1/ko
Priority to CN202110696540.8A priority patent/CN113318239B/zh
Priority to EP15806443.6A priority patent/EP3154586B1/en
Priority to CA2950926A priority patent/CA2950926A1/en
Priority to JP2016572717A priority patent/JP6695286B2/ja
Priority to US15/030,567 priority patent/US20160250351A1/en
Priority to CN201580031452.9A priority patent/CN106573051B/zh
Priority to BR112016029123A priority patent/BR112016029123A2/pt
Application filed by Mayo Foundation for Medical Education and Research, Mayo Clinic in Florida filed Critical Mayo Foundation for Medical Education and Research
Priority to AU2015274408A priority patent/AU2015274408A1/en
Priority to RU2017100445A priority patent/RU2708332C2/ru
Publication of WO2015191969A1 publication Critical patent/WO2015191969A1/en
Priority to IL249454A priority patent/IL249454B/en
Anticipated expiration legal-status Critical
Priority to US15/452,669 priority patent/US12403119B2/en
Priority to AU2021200489A priority patent/AU2021200489A1/en
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/282—Platinum compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/38—Albumins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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    • 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
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    • A61K47/6835—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6849—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
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    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6927—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
    • A61K47/6929—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2887—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
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    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • C—CHEMISTRY; METALLURGY
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    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
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Definitions

  • lymphomas e.g., mature B-cell neoplasms, mature T cell neoplasms, mature natural killer cell neoplasms, immunodeficiency-associated lymphoproliferative disorders, Hodgkin lymphomas, and non-Hodgkin lymphomas.
  • lymphomas e.g., mature B-cell neoplasms, mature T cell neoplasms, mature natural killer cell neoplasms, immunodeficiency-associated lymphoproliferative disorders, Hodgkin lymphomas, and non-Hodgkin lymphomas.
  • this document relates to methods and materials involved in using complexes containing albumin-containing nanoparticles (e.g., ABRAXANE ® nanoparticles) and antibodies (e.g., anti-CD20 polypeptide antibodies such as Rituximab) to treat lymphomas.
  • albumin-containing nanoparticles e.g., ABRAXANE ® nanoparticles
  • Lymphomas are blood cancers that occur when B or T lymphocytes become cancerous. They can develop in the lymph nodes, spleen, bone marrow, blood, or other organs and eventually form a tumor.
  • lymphomas e.g., mature B-cell neoplasms, mature T cell neoplasms, mature natural killer cell neoplasms, immunodeficiency-associated lymphoproliferative disorders, Hodgkin lymphomas, and non-Hodgkin lymphomas.
  • this document provides methods and materials for using complexes containing albumin-containing nanoparticles (e.g., ABRAXANE ® nanoparticles) and antibodies (e.g., anti-CD20 polypeptide antibodies such as Rituximab) to treat lymphomas.
  • albumin-containing nanoparticles e.g., ABRAXANE ® nanoparticles
  • antibodies e.g., anti-CD20 polypeptide antibodies such as Rituximab
  • ABRAXANE ® is available from Celgene Corp. and is a nanoparticle formulation that combines paclitaxel with human albumin.
  • Anti-CD20 polypeptide antibodies such as Rituximab are available from Genentech Inc., Roche, and Aryogen Biopharma under trade names such as RituxanTM, MabTheraTM, and ZytuxTM.
  • Rituximab is a chimeric monoclonal antibody against CD20 polypeptides presents on surface of lymphocyte cells (see, e.g., U.S. Patent No. 5,736,137).
  • albumin-containing nanoparticles e.g., albumin-containing nanoparticles
  • ABRAXANE ® nanoparticles and antibodies can result in the formation of macromolecular complexes, the characteristics of which (e.g., size, antibody content, or chemotherapeutic drug content) can be customized depending on need.
  • macromolecular complexes can retain antibody mediated target binding specificity, can retain or exhibit enhanced chemotherapeutic tumor cell cytotoxicity, and can exhibit no additional toxicity beyond that of ABRAXANE ® nanoparticles alone.
  • contacting ABRAXANE ® with an anti-CD20 polypeptide antibody e.g., Rituximab
  • an anti-CD20 polypeptide antibody e.g., Rituximab
  • a human e.g., a human lymphoma cancer patient
  • a complex that, when administered as a complex, has an increased ability to treat lymphoma as compared to a treatment regimen that includes administering ABRAXANE ® and the anti-CD20 polypeptide antibody separately in a manner that does not form ABRAXANE ® /anti-CD20 polypeptide antibody complexes.
  • the methods and materials provided herein can be used to increase the progression-free survival rate in lymphoma patients. Increasing progression-free survival can allow lymphoma cancer patients to live longer.
  • one aspect of this document features a method for treating a mammal having lymphoma.
  • the method comprises, or consisting essentially of, administering to the mammal a composition comprising nanoparticles containing albumin and placitaxel complexed with an anti-CD20 polypeptide antibody under conditions wherein the length of progression- free survival is increased.
  • the mammal can be a human.
  • the lymphoma can be a Hodgkin lymphomas.
  • the composition can comprise Rituximab complexed with the nanoparticles.
  • the composition can comprise an alkylating agent complexed with the nanoparticles.
  • the alkylating agent can be a platinum compound.
  • the platinum compound can be carboplatin.
  • the anti-CD20 polypeptide antibody can be a humanized antibody.
  • the anti-CD20 polypeptide antibody can be a chimeric antibody.
  • the composition can be administered by injection.
  • the progression-free survival can be increased by 15 percent.
  • the progression-free survival can be increased by 25 percent.
  • the progression-free survival can be increased by 50 percent.
  • the progression- free survival can be increased by 75 percent.
  • the progression- free survival can be increased by 100 percent.
  • the composition can be administered under conditions wherein the time to progression is increased.
  • this document features a method for treating a mammal having lymphoma.
  • the method comprises, or consists essentially of, administering, to the mammal, a composition comprising albumin-containing nanoparticle/antibody complexes, wherein the average diameter of the complexes is between 0.1 and 0.9 ⁇ , and wherein the antibody is an anti-CD20 antibody.
  • the mammal can be a human.
  • the lymphoma can be a mature B-cell neoplasm.
  • the lymphoma can be a mature T cell neoplasm.
  • the lymphoma can be a Hodgkin lymphoma.
  • the albumin-containing nanoparticle/antibody complexes can be ABRAXANE ® / Rituximab complexes.
  • the composition or the albumin-containing nanoparticle/antibody complexes can comprise an alkylating agent.
  • the alkylating agent can be a platinum compound.
  • the platinum compound can be carboplatin.
  • the composition can comprise an anti-inflammatory agent.
  • the anti-CD20 polypeptide antibodies can be humanized antibodies.
  • the anti- CD20 polypeptide antibodies can be chimeric antibodies.
  • the composition can be administered by injection.
  • the administration of the composition can be effective to increase progression-free survival by 25 percent.
  • the administration of the composition can be effective to increase progression- free survival by 50 percent.
  • the administration of the composition can be effective to increase progression-free survival by 75 percent.
  • the administration of the composition can be effective to increase progression-free survival by 100 percent.
  • the administration of the composition can be under conditions wherein the median time to progression for a population of mammals with the lymphoma is at least 150 days.
  • the administration of the composition can be under conditions wherein the median time to progression for a population of mammals with the lymphoma is at least 165 days.
  • the administration of the composition can be under conditions wherein the median time to progression for a population of mammals with the lymphoma is at least 170 days.
  • the average diameter of the complexes can be from 0.1 ⁇ to 0.3 ⁇ .
  • the average diameter of the complexes can be from 0.15 ⁇ to 0.3 ⁇ .
  • the average diameter of the complexes can be from 0.2 ⁇ to 0.5 ⁇ .
  • the average diameter of the complexes can be from 0.3 ⁇ to 0.5 ⁇ .
  • the average diameter of the complexes can be from 0.2 ⁇ to 0.8 ⁇ .
  • the average diameter of the complexes can
  • this document features a method for treating a mammal having lymphoma.
  • the method comprises, or consists essentially of, administering, to the mammal, a composition comprising albumin-containing nanoparticle/antibody complexes, wherein the average diameter of at least 5 percent of the complexes of the composition is between 0.1 and 0.9 ⁇ , and wherein the antibodies are anti-CD20 antibodies.
  • the mammal can be a human.
  • the lymphoma can be a mature B-cell neoplasm.
  • the lymphoma can be a mature T cell neoplasm.
  • the lymphoma can be a Hodgkin lymphoma.
  • albumin-containing nanoparticle/antibody complexes can be ABRAXANE®/ Rituximab complexes.
  • the composition or the albumin-containing nanoparticle/antibody complexes can comprise an alkylating agent.
  • the alkylating agent can be a platinum compound.
  • the platinum compound can be carboplatin.
  • the composition can comprise an anti-inflammatory agent.
  • the anti-CD20 polypeptide antibodies can be humanized antibodies.
  • the anti- CD20 polypeptide antibodies can be chimeric antibodies.
  • the composition can be administered by injection.
  • the administration of the composition can be effective to increase progression-free survival by 25 percent.
  • the administration of the composition can be effective to increase progression- free survival by 50 percent.
  • the administration of the composition can be effective to increase progression-free survival by 75 percent.
  • the administration of the composition can be effective to increase progression-free survival by 100 percent.
  • the administration of the composition can be under conditions wherein the median time to progression for a population of mammals with the lymphoma is at least 150 days.
  • the administration of the composition can be under conditions wherein the median time to progression for a population of mammals with the lymphoma is at least 165 days.
  • the administration of the composition can be under conditions wherein the median time to progression for a population of mammals with the lymphoma is at least 170 days.
  • the average diameter of at least 5 percent of the complexes of the composition can be from 0.2 ⁇ to 0.9 ⁇ .
  • the average diameter of at least 5 percent of the complexes of the composition can be from 0.2 ⁇ to 0.8 ⁇ .
  • the average diameter of at least 5 percent of the complexes of the composition can be from 0.2 ⁇ to 0.7 ⁇ .
  • the average diameter of at least 5 percent of the complexes of the composition can be from 0.2 ⁇ to 0.6 ⁇ .
  • the average diameter of at least 5 percent of the complexes of the composition can be from 0.2 ⁇ to 0.5 ⁇ .
  • the average diameter of at least 5 percent of the complexes of the composition can be from 0.2 ⁇ to 0.4 ⁇ .
  • the average diameter of at least 10 percent of the complexes of the composition can be between 0.1 and 0.9 ⁇ .
  • the average diameter of at least 50 percent of the complexes of the composition can be between 0.1 and 0.9 ⁇ .
  • the average diameter of at least 75 percent of the complexes of the composition can be between 0.1 and 0.9 ⁇ .
  • the average diameter of at least 90 percent of the complexes of the composition can be between 0.1 and 0.9 ⁇ .
  • Figure 1 is a graph plotting the particle size distribution for ABRAXANE ® (ABX) dissolved in Rituxan (RIT) as determined using a Mastersizer 2000E (Malvern Instruments Ltd., Worcestershire, England). ABX (10 mg/mL) was reconstituted in 1 mL of the indicated amount of RIT, and the mixtures were incubated at room temperature for 30 minutes.
  • Figure 2 is a graph plotting percent change at seven days in tumor size from baseline of lymphoma (Daudi cell line) tumor bearing nude mice treated with PBS, Rituxan (RIT; 12 mg/kg) only, ABRAXANE ® (30 mg/kg) only, Rituxan (RIT; 12 mg/kg) followed by ABRAXANE ® (30 mg/kg) one day later, or AR160 complexes (0.159 ⁇ ; complexes where ABRAXANE ® (10 mg/mL) was premixed with 2 mg/mL Rituxan and incubated for 60 minutes before injection).
  • Figure 3 is a Kaplan Meier graph plotting survival of lymphoma (Daudi cell line) tumor bearing nude mice treated with PBS, Rituxan (RIT; 12 mg/kg) only,
  • ABRAXANE ® (30 mg/kg) only, Rituxan (RIT; 12 mg/kg) followed by ABRAXANE ® (30 mg/kg) one day later, or AR160 complexes (0.159 ⁇ ; complexes where
  • ABRAXANE ® (10 mg/mL) was premixed with 2 mg/mL Rituxan and incubated for 60 minutes before injection).
  • this document provides methods and materials for using complexes containing albumin-containing nanoparticles (e.g., ABRAXANE ® nanoparticles) and antibodies (e.g., anti-CD20 polypeptide antibodies such as Rituximab) to treat lymphomas.
  • albumin-containing nanoparticles e.g., ABRAXANE ® nanoparticles
  • antibodies e.g., anti-CD20 polypeptide antibodies such as Rituximab
  • the methods and materials provided herein can be used to treat any type of lymphoma.
  • the methods and materials provided herein can be used to treat mature B-cell neoplasms, mature T cell neoplasms, mature natural killer cell neoplasms, immunodeficiency-associated lymphoproliferative disorders, Hodgkin lymphomas, or non-Hodgkin lymphomas.
  • the methods and materials provided herein can be used to treat lymphomas in any type of mammal including, without limitation, mice, rats, dogs, cats, horses, cows, pigs, monkeys, and humans.
  • complexes containing albumin-containing nanoparticles e.g., ABRAXANE ® nanoparticles
  • antibodies e.g., anti-CD20 polypeptide antibodies such as Rituximab
  • albumin-containing nanoparticles and antibodies can be designed to have an average diameter that is greater than 1 ⁇ .
  • appropriate concentrations of albumin-containing nanoparticles and antibodies can be used such that complexes having an average diameter that is greater than 1 ⁇ are formed.
  • manipulations such as centrifugation can be used to form preparations of albumin-containing nanoparticle/antibody complexes where the average diameter of those complexes is greater than 1 ⁇ .
  • the average diameter of those complexes is greater than 1 ⁇ .
  • preparations of albumin-containing nanoparticle/antibody complexes provided herein can have an average diameter that is between 1 ⁇ and 5 ⁇ (e.g., between 1.1 ⁇ and 5 ⁇ , between 1.5 ⁇ and 5 ⁇ , between 2 ⁇ and 5 ⁇ , between 2.5 ⁇ and 5 ⁇ , between
  • nanoparticle/antibody complexes provided herein having an average diameter that is between 1 ⁇ and 5 ⁇ can be administered systemically (e.g., intravenously) to treat lymphomas located within a mammal's body.
  • the preparations of albumin-containing nanoparticle/antibody complexes provided herein can have an average diameter that is between 5 ⁇ and 50 ⁇ (e.g., between 6 ⁇ and 50 ⁇ , between 7 ⁇ and 50 ⁇ , between 10 ⁇ and 50 ⁇ , between 15 ⁇ and 50 ⁇ , between 20 ⁇ and 50 ⁇ , between 25 ⁇ and 50 ⁇ , between 30 ⁇ and 50 ⁇ , between 35 ⁇ and 50 ⁇ , between 5 ⁇ and 45 ⁇ , between 5 ⁇ m and 40 ⁇ , between 5 ⁇ m and 35 ⁇ , between 5 ⁇ and 30 ⁇ m, between 5 ⁇ and 25 ⁇ m, between 5 ⁇ and 20 ⁇ , between 5 ⁇ m and 15 ⁇ , or between 10 ⁇ and 30 ⁇ m).
  • Preparations of albumin-containing nanoparticle/antibody complexes provided herein having an average diameter that is between 5 ⁇ and 50 ⁇ can be administered into a tumor (e.g., intratumorally) or in a region of a tumor located within a mammal's body.
  • a preparation of albumin-containing nanoparticle/antibody complexes provided herein can have greater than 60 percent (e.g., greater than 65, 70, 75, 80, 90, 95, or 99 percent) of the complexes having a diameter that is between 1 ⁇ and 5 ⁇ (e.g., between 1.1 ⁇ and 5 ⁇ , between 1.5 ⁇ and 5 ⁇ , between 2 ⁇ and 5 ⁇ , between 2.5 ⁇ and 5 ⁇ , between 3 ⁇ and 5 ⁇ , between 3.5 ⁇ and 5 ⁇ , between 1 ⁇ and 5 ⁇ (e.g., between 1.1 ⁇ and 5 ⁇ , between 1.5 ⁇ and 5 ⁇ , between 2 ⁇ and 5 ⁇ , between 2.5 ⁇ and 5 ⁇ , between 3 ⁇ and 5 ⁇ , between 3.5 ⁇ and 5 ⁇ , between 1 ⁇ and 5 ⁇ (e.g., between 1.1 ⁇ and 5 ⁇ , between 1.5 ⁇ and 5 ⁇ , between 2 ⁇ and 5 ⁇ , between 2.5 ⁇ and 5 ⁇ , between 3
  • Preparation of albumin-containing nanoparticle/antibody complexes provided herein having greater than 60 percent (e.g., greater than 65, 70, 75, 80, 90, 95, or 99 percent) of the complexes with a diameter that is between 1 ⁇ and 5 ⁇ can be administered systemically (e.g., intravenously) to treat lymphomas located within a mammal's body.
  • a preparation of albumin-containing nanoparticle/antibody complexes provided herein can have greater than 60 percent (e.g., greater than 65, 70, 75, 80, 90, 95, or 99 percent) of the complexes having a diameter that is between 5 ⁇ and 50 ⁇ (e.g., between 6 ⁇ and 50 ⁇ , between 7 ⁇ and 50 ⁇ , between 10 ⁇ and 50 ⁇ , between 15 ⁇ and 50 ⁇ , between 20 ⁇ and 50 ⁇ , between 25 ⁇ and 50 ⁇ , between 30 ⁇ and 50 ⁇ , between 35 ⁇ and 50 ⁇ , between 5 ⁇ and 45 ⁇ , between 5 ⁇ and 40 ⁇ , between 5 ⁇ and 35 ⁇ , between 5 ⁇ and 30 ⁇ , between 5 ⁇ and 25 ⁇ , between 5 ⁇ and 20 ⁇ , between 5 ⁇ and 15 ⁇ , or between 10 ⁇ and 30 ⁇ ).
  • 5 ⁇ and 50 ⁇ e.g., between 6 ⁇ and 50 ⁇ , between 7 ⁇ and 50 ⁇ , between
  • Preparation of albumin-containing nanoparticle/antibody complexes provided herein having greater than 60 percent (e.g., greater than 65, 70, 75, 80, 90, 95, or 99 percent) of the complexes with a diameter that is between 5 ⁇ and 50 ⁇ can be administered into a tumor (e.g., intratumorally) or in a region of a tumor located within a mammal's body.
  • complexes containing albumin-containing nanoparticles e.g., ABRAXANE ® nanoparticles
  • antibodies e.g., anti-CD20 polypeptide antibodies such as Rituximab
  • albumin-containing nanoparticles and antibodies can be designed to have an average diameter that is less than 1 ⁇ .
  • appropriate concentrations of albumin-containing nanoparticles and antibodies e.g., Rituximab
  • complexes having an average diameter that is less than 1 ⁇ are formed.
  • the preparations of albumin-containing nanoparticle/antibody complexes provided herein can have an average diameter that is between 0.1 ⁇ and 1 ⁇ (e.g., between 0.1 ⁇ and 0.95 ⁇ , between 0.1 ⁇ and 0.9 ⁇ , between 0.1 ⁇ and 0.8 ⁇ , between 0.1 ⁇ and 0.7 ⁇ , between 0.1 ⁇ and 0.6 ⁇ , between 0.1 ⁇ and 0.5 ⁇ , between 0.1 ⁇ and 0.4 ⁇ , between 0.1 ⁇ and 0.3 ⁇ , between 0.1 ⁇ and 0.2 ⁇ , between 0.2 ⁇ and 1 ⁇ , between 0.3 ⁇ and 1 ⁇ , between 0.4 ⁇ and 1 ⁇ , between 0.5 ⁇ and 1 ⁇ , between 0.2 ⁇ and 0.6 ⁇ , between 0.3 ⁇ and 0.6 ⁇ , between 0.2 ⁇ and 0.5 ⁇ , or between 0.3 ⁇ and 0.5 ⁇ ).
  • lymphomas located within a mammal's body are administered systemically (e.g., intravenously) to treat lymphomas located within a mammal's body.
  • a preparation of albumin-containing nanoparticle/antibody complexes provided herein can have greater than 60 percent (e.g., greater than 65, 70, 75, 80, 90, 95, or 99 percent) of the complexes having a diameter that is between 0.1 ⁇ and 0.9 ⁇ (e.g., between 0.1 ⁇ and 0.95 ⁇ , between 0.1 ⁇ and 0.9 ⁇ , between 0.1 ⁇ and 0.8 ⁇ , between 0.1 ⁇ and 0.7 ⁇ , between 0.1 ⁇ and 0.6 ⁇ , between 0.1 ⁇ and 0.5 ⁇ , between 0.1 ⁇ and 0.4 ⁇ , between 0.1 ⁇ and 0.3 ⁇ , between 0.1 ⁇ and 0.2 ⁇ , between 0.2 ⁇ and 1 ⁇ , between 0.3 ⁇ and 1 ⁇ , between 0.4 ⁇ and 1 ⁇ , between 0.5 ⁇ and 1 ⁇ , between 0.2 ⁇ and 0.6 ⁇ , between 0.3 ⁇ and 0.6 ⁇ m, between 0.2 ⁇ and 0.5 ⁇ m, between 0.2
  • Preparation of albumin- containing nanoparticle/antibody complexes provided herein having greater than 60 percent (e.g., greater than 65, 70, 75, 80, 90, 95, or 99 percent) of the complexes with a diameter that is between 0.1 ⁇ and 0.9 ⁇ can be administered systemically (e.g., intravenously) to treat cancers located within a mammal's body.
  • albumin-containing nanoparticles such as ABRAXANE ® can be contacted with an antibody such as an anti-CD20 polypeptide antibody (e.g., Rituximab) prior to administration to a human to form an albumin-containing nanoparticle/antibody complex (e.g., an ABRAXANE ® /anti-CD20 polypeptide antibody complex).
  • an antibody such as an anti-CD20 polypeptide antibody (e.g., Rituximab)
  • Any appropriate albumin-containing nanoparticle preparation and any appropriate antibody can be used as described herein.
  • ABRAXANE ® nanoparticles can be used as described herein.
  • antibodies that can be used to form albumin-containing nanoparticle/antibody complexes as described herein include, without limitation,
  • Rituximab (e.g., RituxanTM, MabTheraTM, or ZytuxTM).
  • an appropriate dose of ABRAXANE ® and an appropriate dose of Rituximab can be mixed together in the same container. This mixture can be incubated at an appropriate temperature (e.g., room temperature, between 15 °C and 30 °C, between 15 °C and 25 °C, between 20 °C and 30 °C, or between 20 °C and 25 °C) for a period of time (e.g., about 30 minutes, or between about 5 minutes and about 60 minutes, between about 5 minutes and about 45 minutes, between about 15 minutes and about 60 minutes, between about 15 minutes and about 45 minutes, between about 20 minutes and about 400 minutes, or between about 25 minutes and about 35 minutes) before being administered to a cancer patient (e.g., a lymphoma patient).
  • a cancer patient e.g., a lymphoma patient
  • ABRAXANE ® can be contacted with an anti-CD20 polypeptide antibody by injecting both ABRAXANE ® and the anti-CD20 polypeptide antibody either individually or as a pre-mixed combination into an IV bag containing an IV bag solution.
  • the contents of the IV bag including ABRAXANE ® /anti-CD20 polypeptide antibody complexes can be introduced into the patient to be treated.
  • albumin-containing nanoparticles such as ABRAXANE ® can be contacted with an antibody such as an anti-CD20 polypeptide antibody (e.g., Rituximab) to form albumin-containing nanoparticle/antibody complexes (e.g., ABRAXANE ® /anti- CD20 polypeptide antibody complexes) that are stored prior to being administered to a cancer patient (e.g., a lymphoma patient).
  • a composition containing albumin-containing nanoparticle/antibody complexes can be formed as described herein and stored for a period of time (e.g., days or weeks) prior to being administered to a cancer patient.
  • albumin-containing nanoparticles such as ABRAXANE ® and an antibody such as an anti-CD20 polypeptide antibody.
  • ABRAXANE ® can be obtained from Celgene Corp. or as described elsewhere (U.S. Patent No. 6,537,579).
  • Rituximab can be obtained from Genentech Corp. or Roche Corp. or as described elsewhere (U.S. Patent No. 5,736,137).
  • an albumin-containing nanoparticle such as ABRAXANE ® and an antibody such as anti-CD20 polypeptide antibody can include one or more other agents such as an alkylating agent (e.g., a platinum compound).
  • an alkylating agent e.g., a platinum compound
  • platinum compounds that can be used as an alkylating agent include, without limitation, carboplatin (PARAPLATIN ® ), cisplatin (PLATINOL ® ), oxaliplatin
  • albumin-containing nanoparticle/antibody complex examples include, without limitation, adriamycin, cyclophosphamide, vincristine, prednisone, dexamethasone, cytarabine, methotrexate, thiotepa, ifosfamide, chlorambucil, dacarbazine, bleomycin, ibrutinib, campath-B, gemcitabine, revlimid, sirolimus, temsirolimus, bexxar, brentuximab, bendamustine, and etoposide.
  • an albumin-containing nanoparticle/antibody complex provided herein can include brentuximab, cyclophosphamide, adriamycin, or vincristine as part of the complex.
  • albumin-containing nanoparticle/antibody complex provided herein (e.g., ABRAXANE ® /anti-CD20 polypeptide antibody complexes)
  • a composition containing albumin-containing nanoparticle/antibody complexes such as ABRAXANE ® /anti-CD20 polypeptide antibody complexes can be administered via injection (e.g., subcutaneous injection, intramuscular injection, intravenous injection, or intrathecal injection).
  • nanoparticle/antibody complex provided herein e.g., ABRAXANE ® /anti-CD20 polypeptide antibody complexes
  • the mammal can be assessed to determine whether or not the mammal has lymphoma. Any appropriate method can be used to determine whether or not a mammal has lymphoma.
  • a mammal e.g., human
  • tissue biopsy e.g., lymph node tissue sample
  • lymphoma a tissue biopsy (e.g., lymph node tissue sample) can be collected and analyzed to determine whether or not a mammal has lymphoma.
  • the mammal After identifying a mammal as having lymphoma, the mammal can be
  • compositions containing albumin-containing nanoparticle/antibody complexes provided herein e.g., ABRAXANE ® /anti-CD20 polypeptide antibody complexes.
  • a composition containing ABRAXANE ® /anti-CD20 polypeptide antibody complexes can be administered prior to or in lieu of surgical resection of a tumor.
  • a composition containing albumin-containing nanoparticle/antibody complexes provided herein e.g., ABRAXANE ® /anti-CD20 polypeptide antibody complexes
  • a composition containing albumin-containing nanoparticle/antibody complexes provided herein can be administered to a mammal in any appropriate amount, at any appropriate frequency, and for any appropriate duration effective to achieve a desired outcome (e.g., to increase progression- free survival).
  • a composition containing albumin-containing nanoparticle/antibody complexes provided herein can be administered to a mammal having lymphoma to reduce the progression rate of the lymphoma by 5, 10, 25, 50, 75, 100, or more percent.
  • the progression rate can be reduced such that no additional cancer progression is detected.
  • Any appropriate method can be used to determine whether or not the progression rate of lymphoma is reduced.
  • the progression rate of lymphoma can be assessed by imaging tissue at different time points and determining the amount of cancer cells present. The amounts of cancer cells determined within tissue at different times can be compared to determine the progression rate. After treatment as described herein, the progression rate can be determined again over another time interval.
  • the stage of cancer (e.g., lymphoma) after treatment can be determined and compared to the stage before treatment to determine whether or not the progression rate was reduced.
  • nanoparticle/antibody complexes provided herein can be administered to a mammal having lymphoma under conditions where progression-free survival is increased (e.g., by 5, 10, 25, 50, 75, 100, or more percent) as compared to the median progression- free survival of
  • ABRAXANE ® /antibody complexes e.g., without forming ABRAXANE ® /anti-CD20 polypeptide antibody complexes.
  • a composition containing albumin- containing nanoparticle/antibody complexes provided herein can be administered to a mammal having lymphoma to increase progression-free survival by 5, 10, 25, 50, 75, 100, or more percent as compared to the median progression- free survival of corresponding mammals having lymphoma and having received ABRAXANE ® or an antibody (e.g., an anti-CD20 polypeptide antibody) alone.
  • Progression-free survival can be measured over any length of time (e.g., one month, two months, three months, four months, five months, six months, or longer).
  • nanoparticle/antibody complexes provided herein can be administered to a mammal having lymphoma under conditions where the 8-week progression-free survival rate for a population of mammals is 65% or greater (e.g., 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80% or greater) than that observed in a population of comparable mammals not receiving a composition containing albumin-containing nanoparticle/antibody complexes provided herein (e.g., ABRAXANE ® /anti-CD20 polypeptide antibody complexes).
  • ABRAXANE ® /anti-CD20 polypeptide antibody complexes can be administered to a mammal having lymphoma under conditions where the 8-week progression-free survival rate for a population of mammals is 65% or greater (e.g., 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%
  • composition containing albumin- containing nanoparticle/antibody complexes provided herein can be administered to a mammal having lymphoma under conditions where the median time to progression for a population of mammals is at least 150 days (e.g., at least 155, 160, 163, 165, or 170 days).
  • nanoparticle/antibody complexes provided herein can be any amount that reduces the progression rate of lymphoma, increases the progression-free survival rate, or increases the median time to progression without producing significant toxicity to the mammal.
  • an effective amount of ABRAXANE ® can be from about 50 mg/m 2 to about 150 mg/m 2 (e.g., about 80 mg/m 2 )
  • an effective amount of an anti-CD20 polypeptide antibody such as Rituximab can be from about 5 mg/kg to about 20 mg/kg (e.g., about 10 mg/kg or 375 mg/m 2 ).
  • the amount of ABRAXANE ® or anti-CD20 polypeptide antibody can be increased by, for example, two fold. After receiving this higher concentration, the mammal can be monitored for both responsiveness to the treatment and toxicity symptoms, and adjustments made accordingly.
  • the effective amount can remain constant or can be adjusted as a sliding scale or variable dose depending on the mammal's response to treatment. Various factors can influence the actual effective amount used for a particular application. For example, the frequency of administration, duration of treatment, use of multiple treatment agents, route of administration, and severity of the lymphoma may require an increase or decrease in the actual effective amount administered.
  • the frequency of administration can be any frequency that reduces the progression rate of lymphoma, increases the progression- free survival rate, or increases the median time to progression without producing significant toxicity to the mammal.
  • the frequency of administration can be from about once a month to about three times a month, or from about twice a month to about six times a month, or from about once every two months to about three times every two months.
  • the frequency of administration can remain constant or can be variable during the duration of treatment.
  • a course of treatment with a composition containing ABRAXANE ® /anti-CD20 polypeptide antibody complexes can include rest periods.
  • composition containing ABRAXANE ® /anti-CD20 polypeptide antibody complexes can be administered over a two week period followed by a two week rest period, and such a regimen can be repeated multiple times.
  • the effective amount various factors can influence the actual frequency of administration used for a particular application. For example, the effective amount, duration of treatment, use of multiple treatment agents, route of administration, and severity of the lymphoma may require an increase or decrease in administration frequency.
  • An effective duration for administering a composition provided herein can be any duration that reduces the progression rate of lymphoma, increases the progression-free survival rate, or increases the median time to progression without producing significant toxicity to the mammal.
  • the effective duration can vary from several days to several weeks, months, or years.
  • the effective duration for the treatment of lymphoma can range in duration from several weeks to several months.
  • an effective duration can be for as long as an individual mammal is alive. Multiple factors can influence the actual effective duration used for a particular treatment.
  • an effective duration can vary with the frequency of administration, effective amount, use of multiple treatment agents, route of administration, and severity of the lymphoma.
  • a composition containing albumin-containing nanoparticle/antibody complexes provided herein can be in any appropriate form.
  • a composition provided herein can be in the form of a solution or powder with or without a diluent to make an injectable suspension.
  • a composition also can contain additional ingredients including, without limitation, pharmaceutically acceptable vehicles.
  • a pharmaceutically acceptable vehicle can be, for example, saline, water, lactic acid, mannitol, or combinations thereof.
  • the mammal After administering a composition provided herein to a mammal, the mammal can be monitored to determine whether or not the lymphoma was treated. For example, a mammal can be assessed after treatment to determine whether or not the progression rate of lymphoma was reduced (e.g., stopped). As described herein, any method can be used to assess progression and survival rates.
  • a formulation of ABRAXANE ® / Rituxan complexes described in Example 1 can be administered to a human lymphoma patient as described in the methods set forth in Example 3.
  • nanoparticles containing albumin e.g., nanoparticles with an albumin shell
  • an agent other than placitaxel can be used as described herein in place of or in combination with ABRAXANE ® .
  • albumin-containing albumin e.g., albumin-containing albumin and an agent other than placitaxel
  • nanoparticles designed to carry a cancer chemotherapeutic agent can be used to form nanoparticle/anti-CD20 polypeptide antibody complexes that can be used as described herein.
  • a cancer chemotherapeutic agent includes, without limitation, vinblastine.
  • a composition can be formulated to include nanoparticles containing albumin (e.g., nanoparticles with an albumin shell) that are conjugated to an antibody, agent, or combination of antibodies and agents to form complexes for treating lymphoma.
  • albumin e.g., nanoparticles with an albumin shell
  • albumin nanoparticles can be formulated to include adriamycin, cyclophosphamide, vincristine, prednisone, dexamethasone, cytarabine, methotrexate, thiotepa, ifosfamide, chlorambucil, dacarbazine, bleomycin, ibrutinib, campath-B, gemcitabine, revlimid, sirolimus, temsirolimus, bexxar, brentuximab, bendamustine, etoposide, or combinations thereof with or without including rituximab.
  • nanoparticles containing albumin e.g., nanoparticles with an albumin shell
  • a complex described herein e.g., ABRAXANE ® / rituximab complexes
  • steroidal anti- inflammatory agents e.g., prednisone
  • non-steroidal anti-inflammatory agents e.g., naproxen
  • lympho-depleting cytotoxic agents e.g., cyclophosphamide
  • immune cell and/or cytokine targeting antibodies e.g., infliximab
  • a combination thereof can be incorporated into nanoparticles containing albumin or ABRAXANE ® / rituximab complexes.
  • anti-IL-4 agents e.g., anti-IL-4 antibodies
  • anti-IL-13 agents e.g., soluble IL-13 receptor
  • combinations thereof can be incorporated into nanoparticles containing albumin or ABRAXANE ® / rituximab complexes.
  • cytokine profiles e.g., IL-4, IL-13, IL-4, IL-13, IL-5, IL-10, IL-2, and interferon gamma
  • cytokine profiles e.g., IL-4, IL-13, IL-4, IL-13, IL-5, IL-10, IL-2, and interferon gamma
  • Example 1 Making ABRAXANE ® / Rituxan ® complexes ABRAXANE ® was incubated with various increasing concentrations of Rituxan ® (rituximab) to form ABRAXANE ® / Rituxan ® complexes of increasing diameter. Ten milligrams of ABRAXANE ® was reconstituted in 1 mL of Rituxan ® at 0, 2, 4, 6, 8, and 10 mg/mL, and the mixture was incubated at room temperature for 30 minutes. After incubation, the distributions of particle sizes were determined with the Mastersizer 2000. The median particle size ranged from 0.147 ⁇ to 8.286 ⁇ for 0 and 10 mg/mL Rituxan ® , respectively ( Figure 1).
  • mice Female athymic nude mice were injected with lxl 0 6 lymphoma cells (Daudi cell line). Tumors were allowed to grow, and treatments were administered when tumors were between 800 and 1000 mm 3 .
  • Mice were treated with (a) a single dose of 100 PBS on day 0, (b) a single dose of Rituxan (12 mg/kg) on day 0, (c) a single dose of ABRAXANE ® (30 mg/kg) on day 0, (d) a single dose of Rituxan (12 mg/kg) on day 0 followed by a single dose of ABRAXANE ® (30 mg/kg) on day 1, or (e) a single dose of AR160 (equivalent to 30 mg/kg of ABRAXANE ® ) on day 0. Tumor volumes (mm 3 ) were monitored, and the percent change in tumor volume seven days after treatment was determined.
  • the AR160 complexes were produced as follows. 10 mg ABRAXANE ® was reconstituted in 2 mg of Rituxan in 500 0.9% saline and incubated for 1 hour at room temperature. After incubation, AR160 was brought to 1 mL with 0.9% saline. AR160 was further diluted, and 100 was administered to mice at a dose equivalent to 12 mg/kg Rituxan and 30 mg/kg ABRAXANE ® . Average particle size for AR160 was 0.159 ⁇ .
  • the maximum tolerated dose is defined as the highest dose level among those tested where at most one out of six patients develops a DLT prior to the start of their second cycle of treatment and the next highest dose level is such that two out of a maximum of six patients treated at this dose level developed a DLT prior to the start of their second cycle of treatment.
  • a minimum of two or a maximum of six patients are accrued to a given dose level.
  • dose level 1 (and if accrued to, dose levels -1 & -2), enrollment is temporarily halted after each patient has been enrolled in order to gather acute adverse event data over the first cycle of their treatment.
  • dose levels 2 & 3 patients are accrued to these dose levels so that at any given time no more than two patients are receiving their first cycle of treatment and acute adverse event data over the first treatment cycle for all other patients treated at the current dose level is known. If, at any time in the enrollment process, two patients treated at the current dose level develop a DLT during the first cycle of treatment, enrollment is closed to that dose level.
  • Enrollment is re-opened to the next lower dose level if fewer than six patients have been treated at that dose level. If none of the first three patients treated at a given dose level develops a DLT during the first cycle of treatment, enrollment to the dose level is closed and enrollment is reopen at next higher dose level. If there are no other higher dose levels to be tested, three additional patients are enrolled at the current dose level to confirm MTD. If one of the first three patients treated at a given dose level develops a DLT during the first cycle of treatment, three additional patients are enrolled (sequentially) onto the current dose level. If, at any time in the enrollment of these three additional patients, a patient develops a DLT, enrollment is closed to this dose level.
  • Enrollment is re-opened to the next lower dose level if fewer than six patients are treated at that dose level. If none of these three additional patients develops a DLT during the first cycle of treatment, enrollment to this dose level is closed and enrollment is reopened at next higher dose level. If there are no other higher dose levels to be tested, this is considered the MTD.
  • the patient returns for evaluation and retreatment (at least every 28 +/- 3 days) according to the schedule. If a patient fails to complete the first cycle of treatment for reasons other than toxicity, an additional patient is enrolled to replace this patient.
  • Day 8 Omit dose that day. If resolved to ⁇ Grade 2 by day 15, then dose reduce by one level and retreat.
  • Day 15 Omit dose that day.
  • Gastrointestinal Bowel Discontinue all study treatment and proceed to Disorders perforation Event Monitoring
  • treatment may be restarted. If treatment needs to be held >4 weeks, discontinue all study treatment and go to Event Monitoring.
  • Grade 3 • Hold treatment. If the planned duration of full- or dose anticoagulation is ⁇ 2weeks,treatment should asymptomatic be held until the full-dose anticoagulation period Grade 4 is over.
  • the subject must have an in-range INR (usually 2-3) on a stable dose of warfarin, or on stable dose of heparin prior to restarting treatment.
  • the subject must not have pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels or other conditions)
  • G-CSF colony- stimulating factors
  • Prophylactic use of colony-stimulating factors during the study is not allowed.
  • Therapeutic use in patients with serious neutropenic complications such as tissue infection, sepsis syndrome, fungal infection, etc., may be considered at physician discretion.
  • Recombinant erythropoietin to maintain adequate hemoglobin levels and avoid packed red blood cell transfusions is allowed.
  • Patients do not require premedication prior to administration of ABRAXANE ® / Rituxan complexes.
  • treatment with antihistamines, H2 blockers, and corticosteroids is recommended.
  • Patients should be pre- medicated with the typical regimen for paclitaxel regimens for subsequent cycles.
  • premedication may be administered using the premedication regimen the institution typically uses for solvent-based paclitaxel.
  • ABRAXANE ® / Rituxan complexes are prepared as a hazardous low risk product.
  • ABRAXANE ® is supplied as a white to off- white lyophilized powder containing 100 mg of paclitaxel and approximately 900 mg Albumin Human USP (HA) as a stabilizer in a 50 mL, single-use vial. Each vial of the lyophilized product is reconstituted as set forth below. Unreconstituted ABRAXANE ® is stored at controlled room temperature in its carton. Reconstituted ABRAXANE ® is used immediately.
  • Rituxan is classified as an anti-CD20 monoclonal antibody.
  • the dose appropriate number of vials of Rituxan are obtained, and each vial is further diluted per the following directions to 4 mg/mL.
  • the dose appropriate number of ABRAXANE ® (paclitaxel) 100 mg vials is obtained and each vial is reconstituted per the following directions to a final concentration containing 10 mg/mL nanoparticle albumin- bound (nab) paclitaxel. It is not a requirement to use filter needles in the preparation of, or in-line filters during administration. In addition, filters of pore-size less than 15 micrometers are to be avoided. As with other cytotoxic anticancer drugs, caution is exercised in handling
  • ABRAXANE ® The use of gloves is recommended.
  • each vial is gently swirled and/or inverted slowly for at least 2 minutes until complete dissolution of any cake/powder occurs. The generation of foam is avoided.
  • the concentration of each vial is 100 mg/10 mL ABRAXANE ® and 40 mg/10 mL Rituxan.
  • the vials containing the ABRAXANE ® and Rituxan are allowed to sit for 60 minutes.
  • the vial(s) are gently swirled and/or inverted every 10 minutes to continue to mix the complexes.
  • a sterile 60- to 100-mL syringe (appropriate size for the volume being administered) is used to withdraw the calculated dosing volume of ABRAXANE ® and Rituxan from each vial.
  • a sufficient quantity of 0.9% Sodium Chloride Injection, USP is added to make the final concentration of ABRAXANE ® 5 mg/mL and Rituxan 2 mg/mL.
  • the syringe is gently swirled and/or inverted slowly for 1 minute to mix. The storage and stability is for up to 4 hours at room temperature following final dilution.
  • the IV initial complex dose is infused over 60 minutes via syringe pump.
  • the infusion may be shortened to 30 minutes if the initial infusion is well tolerated.
  • Infusion is monitored closely during the infusion process for signs/symptoms of an infusion reaction.
  • the patient's line is flushed after administration with 20 mL 0.9% Sodium Chloride.
  • ABRAXANE ® vials Repeat this procedure for each of the remaining two ABRAXANE ® 100 mg vials.

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BR112016029123A BR112016029123A2 (pt) 2014-06-13 2015-06-12 tratamento de linfomas
CN202110696540.8A CN113318239B (zh) 2014-06-13 2015-06-12 治疗淋巴瘤
EP15806443.6A EP3154586B1 (en) 2014-06-13 2015-06-12 Treating lymphomas
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Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017139698A1 (en) * 2016-02-12 2017-08-17 Mayo Foundation For Medical Education And Research Hematologic cancer treatments
EP3154595A4 (en) * 2014-06-16 2018-01-24 Mayo Foundation for Medical Education and Research Treating myelomas
WO2018027205A1 (en) * 2016-08-05 2018-02-08 Mayo Foundation For Medical Education And Research Modified antibody-albumin nanoparticle complexes for cancer treatment
WO2018045238A1 (en) * 2016-09-01 2018-03-08 Mayo Foundation For Medical Education And Research Methods and compositions for targeting t-cell cancers
US10279036B2 (en) 2012-10-01 2019-05-07 Mayo Foundation For Medical Education And Research Antibody-albumin nanoparticle complexes comprising albumin, bevacizumab, and paclitaxel, and methods of making and using the same
US10300016B2 (en) 2014-10-06 2019-05-28 Mayo Foundation For Medical Education And Research Carrier-antibody compositions and methods of making and using the same
JP2019529388A (ja) * 2016-09-06 2019-10-17 マヨ ファウンデーション フォー メディカル エデュケーション アンド リサーチＭａｙｏ Ｆｏｕｎｄａｔｉｏｎ Ｆｏｒ Ｍｅｄｉｃａｌ Ｅｄｕｃａｔｉｏｎ Ａｎｄ Ｒｅｓｅａｒｃｈ パクリタキセル−アルブミン−結合剤組成物並びに該組成物の使用及び製造方法
EP3432926A4 (en) * 2016-03-21 2019-11-20 Mayo Foundation for Medical Education and Research METHOD FOR REDUCING THE TOXICITY OF CHEMOTHERAPEUTICS
EP3432928A4 (en) * 2016-03-21 2019-11-20 Mayo Foundation for Medical Education and Research PROCESS FOR IMPROVING THE THERAPEUTIC INDEX FOR CHEMOTHERAPEUTIC
JP2019533665A (ja) * 2016-10-10 2019-11-21 アブラクシス バイオサイエンス， エルエルシー ナノ粒子製剤ならびにその作製方法および使用方法
US10561726B2 (en) 2015-10-06 2020-02-18 Vavotar Life Sciences LLC Methods of treating cancer using compositions of antibodies and carrier proteins with antibody pretreatment
US10618969B2 (en) 2016-04-06 2020-04-14 Mayo Foundation For Medical Education And Research Carrier-binding agent compositions and methods of making and using the same
US10765741B2 (en) 2011-05-09 2020-09-08 Mayo Foundation For Medical Education And Research Methods for treating VEGF-expressing cancer using preformed nanoparticle complexes comprising albumin-bound paclitaxel and bevacizumab
EP3749331A4 (en) * 2018-02-06 2021-08-04 Mayo Foundation for Medical Education and Research ANTIBODY PEPTIDE COMPLEX AND THEIR USES
US11241387B2 (en) 2015-08-18 2022-02-08 Mayo Foundation For Medical Education And Research Carrier-binding agent compositions and methods of making and using the same
WO2022051414A1 (en) 2020-09-02 2022-03-10 Mayo Foundation For Medical Education And Research Antibody-nanoparticle complexes and methods for making and using the same
US11427637B2 (en) 2016-09-06 2022-08-30 Mayo Foundation For Medical Education And Research Methods of treating PD-L1 expressing cancer
US11548946B2 (en) 2016-09-01 2023-01-10 Mayo Foundation For Medical Education And Research Carrier-PD-L1 binding agent compositions for treating cancers
US11571469B2 (en) 2016-01-07 2023-02-07 Mayo Foundation For Medical Education And Research Methods of treating cancer with interferon wherein the cancer cells are HLA negative or have reduced HLA expression
US11590098B2 (en) 2016-09-06 2023-02-28 Mayo Foundation For Medical Education And Research Methods of treating triple-negative breast cancer using compositions of antibodies and carrier proteins
US12403119B2 (en) 2014-06-13 2025-09-02 Mayo Foundation For Medical Education And Research Treating lymphomas

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018195416A1 (en) 2017-04-21 2018-10-25 Mayo Foundation For Medical Education And Research Polypeptide-antibody complexes and uses thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5736137A (en) 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US6537579B1 (en) 1993-02-22 2003-03-25 American Bioscience, Inc. Compositions and methods for administration of pharmacologically active compounds
US20110076273A1 (en) * 2009-09-11 2011-03-31 Genentech, Inc. Highly Concentrated Pharmaceutical Formulations
WO2012048223A1 (en) * 2010-10-08 2012-04-12 Abraxis Bioscience, Llc Sparc microenvironment signature, plasma sparc, and ldh as prognostic biomarkers in the treatment of cancer
WO2014055415A1 (en) 2012-10-01 2014-04-10 Mayo Foundation For Medical Education And Research Cancer treatments

Family Cites Families (106)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4350687A (en) 1980-02-10 1982-09-21 Research Corporation Platelet derived cell growth factor
JPS60146833A (ja) 1984-01-10 1985-08-02 Green Cross Corp:The モノクロ−ナル抗体製剤
JPS6178731A (ja) 1985-05-20 1986-04-22 Green Cross Corp:The 加熱処理免疫グロブリン製剤
CA1327161C (en) 1987-09-01 1994-02-22 Mitsugu Kobayashi Lyophilized pharmaceutical composition of neocarzinostatin derivative
SE8801537D0 (sv) 1988-04-26 1988-04-26 Ellco Food Ab Cellodlingsmedium samt forfarande for dess framstellning
US5252713A (en) 1988-09-23 1993-10-12 Neorx Corporation Polymeric carriers for non-covalent drug conjugation
JPH04504253A (ja) 1989-03-27 1992-07-30 セントカー・インコーポレーテツド ＩｇＭ抗体の安定化のための配合物
US5116944A (en) 1989-12-29 1992-05-26 Neorx Corporation Conjugates having improved characteristics for in vivo administration
US5216130A (en) 1990-05-17 1993-06-01 Albany Medical College Complex for in-vivo target localization
WO1994004679A1 (en) 1991-06-14 1994-03-03 Genentech, Inc. Method for making humanized antibodies
US5260308A (en) 1991-11-06 1993-11-09 Mayo Foundation For Medical Education And Research Method to increase permeability of the blood-nerve/brain barriers to proteins
DE69722793T2 (de) 1996-04-26 2004-05-19 Genaera Corp. Squalamin in kombination mit anderen antikrebs-mittelen zur behandlung von tumoren
GB9613182D0 (en) 1996-06-24 1996-08-28 Nycomed Imaging As Method
US6416967B2 (en) 1996-07-12 2002-07-09 Precision Therapeutics, Inc. Method of using multicellular particulates to analyze malignant or hyperproliferative tissue
US5728541A (en) 1996-07-12 1998-03-17 Precision Therapeutics, Inc. Method for preparing cell cultures from biologial specimens for chemotherapeutic and other assays
KR100904931B1 (ko) 1997-06-27 2009-06-29 아브락시스 바이오사이언스, 엘엘씨 나노 입자 및 그의 제조 방법
US8853260B2 (en) 1997-06-27 2014-10-07 Abraxis Bioscience, Llc Formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof
US7041301B1 (en) 1997-11-07 2006-05-09 Mayo Foundation For Medical Education And Research Interferon immunotherapy
US6616925B1 (en) 1998-04-02 2003-09-09 I.D.M. Immuno-Designed Molecules Combined preparation for the treatment of neoplasic diseases or of infectious diseases
US7112409B2 (en) 1999-01-29 2006-09-26 Center For Molecular Medicine And Immunology Method of determining cytokine dosage for myelosuppressive state
US7534866B2 (en) 2005-10-19 2009-05-19 Ibc Pharmaceuticals, Inc. Methods and compositions for generating bioactive assemblies of increased complexity and uses
US6420378B1 (en) 1999-10-15 2002-07-16 Supergen, Inc. Inhibition of abnormal cell proliferation with camptothecin and combinations including the same
DE10132502A1 (de) 2001-07-05 2003-01-23 Gsf Forschungszentrum Umwelt Angriff auf Tumorzellen mit fehlender, niedriger oder anormaler MHC-Expression durch kombinieren von nicht MHC-Restringierten T-Zellen/NK-Zellen und MHC-Restringierten Zellen
IL164287A0 (en) 2002-04-12 2005-12-18 Medarex Inc Methods of treatment using ctla-4 antibodies
EP1578362A4 (en) 2002-07-09 2008-11-05 Point Therapeutics Inc COMBINATION THERAPY WITH A BOROPROLINE COMPOUND
US20040265315A1 (en) 2002-09-05 2004-12-30 Christine Dingivan Methods of preventing or treating T cell malignancies by administering CD2 antagonists
EP1545204B1 (en) 2002-09-06 2016-08-10 THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES Immunotherapy with in vitro-selected antigen-specific lymphocytes after nonmyeloablative lymphodepleting chemotherapy
LT1585548T (lt) 2002-12-09 2018-09-25 Abraxis Bioscience, Llc Farmakologinių agentų kompozicijos ir įvedimo būdai
US20050043233A1 (en) 2003-04-29 2005-02-24 Boehringer Ingelheim International Gmbh Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis
AR046510A1 (es) 2003-07-25 2005-12-14 Regeneron Pharma Composicion de un antagonista de vegf y un agente anti-proliferativo
US8007782B2 (en) 2003-10-22 2011-08-30 The Johns Hopkins University Combination bacteriolytic therapy for the treatment of tumors
BRPI0509927A (pt) 2004-04-22 2007-09-25 Lilly Co Eli composição farmacêutica, uso de uma composição de matéria, e, uso de uma combinação terapeuticamente eficaz de um oligonucleotìdeo anti-sentido de survivina e cloridrato de gemcitabina
WO2005117952A2 (en) * 2004-05-14 2005-12-15 Abraxis Bioscience, Inc. Treatment methods utilizing albumin-binding proteins as targets
US20060067930A1 (en) * 2004-08-19 2006-03-30 Genentech, Inc. Polypeptide variants with altered effector function
US20060204512A1 (en) 2004-09-23 2006-09-14 Vasgene Therapeutics, Inc. Polypeptide compounds for inhibiting angiogenesis and tumor growth
JP2008515915A (ja) 2004-10-07 2008-05-15 エモリー ユニバーシティー 多機能性ナノ粒子結合体およびそれらの使用
US20070166388A1 (en) 2005-02-18 2007-07-19 Desai Neil P Combinations and modes of administration of therapeutic agents and combination therapy
US8735394B2 (en) * 2005-02-18 2014-05-27 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
NZ595313A (en) 2005-02-18 2013-03-28 Abraxis Bioscience Llc The Use Of Nanoparticles Comprising Rapamycin Or Taxane In The Treatment Of Proliferative Diseases
US7976852B2 (en) 2005-04-26 2011-07-12 Eisai R&D Management Co., Ltd. Compositions and methods for cancer immunotherapy
US10183076B2 (en) 2005-05-16 2019-01-22 Resdevco Research And Development Co. L Topical compositions for treatment of irritation of mucous membranes
KR101643416B1 (ko) 2005-08-31 2016-07-27 아브락시스 바이오사이언스, 엘엘씨 증가된 안정성을 가진 수 난용성 약물의 조성물 및 제조방법
CA2880727C (en) 2005-08-31 2019-05-07 Neil P. Desai Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents
US7776832B2 (en) 2006-04-21 2010-08-17 Gem Pharmaceuticals, Llc Anticancer treatment with a combination of taxanes and 13-deoxyanthracyclines
NZ576122A (en) 2006-09-26 2012-09-28 Genmab As Anti-cd38 plus corticosteroids plus a non-corticosteroid chemotherapeutic for treating tumors
EP2081687A2 (en) 2006-10-17 2009-07-29 Koninklijke Philips Electronics N.V. Device for amplification and detection of nucleic acids
EP1914242A1 (en) 2006-10-19 2008-04-23 Sanofi-Aventis Novel anti-CD38 antibodies for the treatment of cancer
GB0621973D0 (en) 2006-11-03 2006-12-13 Philogen Spa Binding molecules and uses thereof
US20100112077A1 (en) * 2006-11-06 2010-05-06 Abraxis Bioscience, Llc Nanoparticles of paclitaxel and albumin in combination with bevacizumab against cancer
AU2007317858A1 (en) * 2006-11-07 2008-05-15 Dow Agrosciences Llc Sprayable, controlled-release, male annihilation technique (MAT) formulation and insect control method
CN102123712B (zh) 2006-12-13 2014-03-19 默沙东公司 使用igf1r抑制剂治疗癌症的方法
KR20150002886A (ko) 2007-03-07 2015-01-07 아브락시스 바이오사이언스, 엘엘씨 항암제로서 라파마이신 및 알부민을 포함하는 나노입자
WO2008112987A1 (en) 2007-03-14 2008-09-18 Mayo Foundation For Medical Education And Research Treating skin cancer
US20110014117A1 (en) 2007-06-28 2011-01-20 Schering Corporation Anti-igf1r
CA2700457A1 (en) 2007-10-01 2009-04-09 Austin Smith Neural tumor stem cells and methods of use thereof
WO2009055343A2 (en) 2007-10-22 2009-04-30 Schering Corporation Fully human anti-vegf antibodies and methods of using
MX2010005104A (es) 2007-11-09 2010-08-04 Peregrine Pharmaceuticals Inc Composiciones de anticuerpo anti-factor de crecimiento endotelial vascular y metodos.
WO2010118365A1 (en) 2009-04-10 2010-10-14 Abraxis Bioscience, Llc Nanoparticle formulations and uses therof
EP2310006A4 (en) 2008-07-03 2012-04-25 Mayo Foundation CANCER TREATMENT
US8119129B2 (en) 2008-08-01 2012-02-21 Bristol-Myers Squibb Company Combination of anti-CTLA4 antibody with dasatinib for the treatment of proliferative diseases
US20110293576A1 (en) 2008-08-04 2011-12-01 Allocure Inc. Mesenchymal stromal cell populations and methods of isolating and using same
WO2010075540A1 (en) 2008-12-23 2010-07-01 Burnham Institute For Medical Research Methods and compositions for synaphically-targeted treatment for cancer
EP3543256A1 (en) 2009-01-12 2019-09-25 Cytomx Therapeutics Inc. Modified antibody compositions, methods of making and using thereof
CA2757645C (en) 2009-04-06 2018-05-15 Mayo Foundation For Medical Education And Research Methods and materials for delivering molecules
US8571805B2 (en) 2009-04-10 2013-10-29 Pharmaco-Kinesis Corporation Method and apparatus for detecting and regulating vascular endothelial growth factor (VEGF) by forming a homeostatic loop employing a half-antibody biosensor
WO2010124009A2 (en) 2009-04-21 2010-10-28 Schering Corporation Fully human anti-vegf antibodies and methods of using
US20120076787A1 (en) 2009-05-28 2012-03-29 Peter Adamson Combination of a tnf-alpha antagonist and a vegf antagonist for use in the treatment or prevention of diseases of the eye
US8345535B2 (en) * 2009-07-13 2013-01-01 Lg Electronics Inc. Method and apparatus for generating ranging preamble code in wireless communication system
BR112012010698A2 (pt) 2009-11-05 2016-11-29 Uab Research Foundation método para tratamento de um sujeito com câncer, método de triagem de uma célula de câncer de mama, e , anticorpo
JP2013510804A (ja) 2009-11-13 2013-03-28 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング 化学療法剤を装荷したナノ粒子に結合した抗インテグリン抗体
CN102740888B (zh) * 2009-11-24 2016-10-12 奥尔德生物制药公司 Il-6抗体及其用途
WO2011100403A1 (en) * 2010-02-10 2011-08-18 Immunogen, Inc Cd20 antibodies and uses thereof
EP3056201A1 (en) 2010-06-07 2016-08-17 Abraxis BioScience, LLC Combination therapy methods for treating proliferative diseases
US9466148B2 (en) 2010-09-03 2016-10-11 Disney Enterprises, Inc. Systems and methods to dynamically adjust an image on a display monitor represented in a video feed
US8992908B2 (en) * 2010-11-23 2015-03-31 Alderbio Holdings Llc Anti-IL-6 antibodies for the treatment of oral mucositis
US20130281377A1 (en) 2010-12-23 2013-10-24 Mayo Foundation For Medical Education And Research Treating multiple myeloma
ES2792062T3 (es) 2011-05-09 2020-11-06 Mayo Found Medical Education & Res Tratamientos contra el cáncer
US20130028895A1 (en) 2011-07-27 2013-01-31 Gerald Wulf Exosome inhibiting agents and uses thereof
US20130071403A1 (en) 2011-09-20 2013-03-21 Vical Incorporated Synergistic anti-tumor efficacy using alloantigen combination immunotherapy
CA2855298A1 (en) 2011-11-09 2013-05-16 The Uab Research Foundation Her3 antibodies and uses thereof
US11471486B2 (en) 2012-09-04 2022-10-18 Inven2 As Selective and controlled expansion of educated NK cells
US10342869B2 (en) 2012-12-07 2019-07-09 The Regents Of The University Of California Compositions comprising anti-CD38 antibodies and lenalidomide
US20140186447A1 (en) 2012-12-28 2014-07-03 Abraxis Bioscience, Llc Nanoparticle compositions of albumin and paclitaxel
SI3049441T1 (sl) 2013-09-27 2020-03-31 F. Hoffmann-La Roche Ag Formulacije protiteles proti PD-L1
AU2015274408A1 (en) 2014-06-13 2017-01-12 Mayo Foundation For Medical Education And Research Treating lymphomas
US10213513B2 (en) 2014-06-16 2019-02-26 Mayo Foundation For Medical Education And Research Treating myelomas
WO2016057554A1 (en) 2014-10-06 2016-04-14 Mayo Foundation For Medical Education And Research Carrier-antibody compositions and methods of making and using the same
US9446148B2 (en) 2014-10-06 2016-09-20 Mayo Foundation For Medical Education And Research Carrier-antibody compositions and methods of making and using the same
WO2016059220A1 (en) 2014-10-16 2016-04-21 INSERM (Institut National de la Santé et de la Recherche Médicale) Tcr-activating agents for use in the treatment of t-all
MX2017007321A (es) 2014-12-02 2017-08-25 Celgene Corp Terapias de combinacion.
CN114796130B (zh) 2015-08-18 2023-10-20 梅约医学教育与研究基金会 载体结合剂组合物及其制备和使用方法
TW201707725A (zh) 2015-08-18 2017-03-01 美國馬友醫藥教育研究基金會 載體－抗體組合物及其製造及使用方法
WO2017176265A1 (en) 2016-04-06 2017-10-12 Mayo Foundation For Medical Education And Research Carrier-binding agent compositions and methods of making and using the same
TW201713360A (en) 2015-10-06 2017-04-16 Mayo Foundation Methods of treating cancer using compositions of antibodies and carrier proteins
US11571469B2 (en) 2016-01-07 2023-02-07 Mayo Foundation For Medical Education And Research Methods of treating cancer with interferon wherein the cancer cells are HLA negative or have reduced HLA expression
US11351254B2 (en) 2016-02-12 2022-06-07 Mayo Foundation For Medical Education And Research Hematologic cancer treatments
CA3018341A1 (en) 2016-03-21 2017-09-28 Mayo Foundation For Medical Education And Research Methods for reducing toxicity of a chemotherapeutic drug
WO2017165439A1 (en) 2016-03-21 2017-09-28 Mayo Foundation For Medical Education And Research Methods for improving the therapeutic index for a chemotherapeutic drug
US10618969B2 (en) 2016-04-06 2020-04-14 Mayo Foundation For Medical Education And Research Carrier-binding agent compositions and methods of making and using the same
RU2019105550A (ru) 2016-08-05 2020-09-07 Мэйо Фаундейшн Фор Медикал Эдьюкейшн Энд Рисерч Модифицированные комплексы с наночастицами антитело-альбумин для лечения злокачественного новообразования
EP3506950A1 (en) 2016-09-01 2019-07-10 Mayo Foundation for Medical Education and Research Methods and compositions for targeting t-cell cancers
CA3035378A1 (en) 2016-09-01 2018-03-08 Mayo Foundation For Medical Education And Research Carrier-pd-l1 binding agent compositions for treating cancers
AU2017324335A1 (en) 2016-09-06 2019-03-28 Mayo Foundation For Medical Education And Research Methods of treating PD-L1 expressing cancer
EP3509635A1 (en) 2016-09-06 2019-07-17 Vavotar Life Sciences LLC Methods of treating triple-negative breast cancer using compositions of antibodies and carrier proteins
EP3509643A1 (en) 2016-09-06 2019-07-17 Mayo Foundation for Medical Education and Research Paclitaxel-albumin-binding agent compositions and methods for using and making the same
JP7142915B2 (ja) 2016-10-28 2022-09-28 株式会社Ｓ＆Ｋバイオファーマ ラクトフェリン／アルブミン融合タンパク質及びその製造方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5736137A (en) 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US6537579B1 (en) 1993-02-22 2003-03-25 American Bioscience, Inc. Compositions and methods for administration of pharmacologically active compounds
US20110076273A1 (en) * 2009-09-11 2011-03-31 Genentech, Inc. Highly Concentrated Pharmaceutical Formulations
WO2012048223A1 (en) * 2010-10-08 2012-04-12 Abraxis Bioscience, Llc Sparc microenvironment signature, plasma sparc, and ldh as prognostic biomarkers in the treatment of cancer
WO2014055415A1 (en) 2012-10-01 2014-04-10 Mayo Foundation For Medical Education And Research Cancer treatments

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
MEZZAROBA ET AL.: "New potential therapeutic approach for the treatment of B- Cell malignancies using chlorambucil/hydroxychloroquine-loaded anti- CD 20 nanoparticles", PLOS ONE, vol. 8, no. 9, 30 September 2013 (2013-09-30), pages 1 - 10, XP055245034 *
See also references of EP3154586A4
WAGNER ET AL.: "Enhanced drug targeting by attachment of an anti-alpha.v integrin antibody to doxorubicin loaded human serum albumin nanoparticles", BIOMATERIALS, vol. 31, no. 8, March 2010 (2010-03-01), pages 2388 - 2398, XP026870608 *

Cited By (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12364754B2 (en) 2011-05-09 2025-07-22 Mayo Foundation For Medical Education And Research Methods for treating VEGF-expressing cancer using preformed nanoparticle complexes comprising albumin-bound paclitaxel and bevacizumab
US10765741B2 (en) 2011-05-09 2020-09-08 Mayo Foundation For Medical Education And Research Methods for treating VEGF-expressing cancer using preformed nanoparticle complexes comprising albumin-bound paclitaxel and bevacizumab
US10376579B2 (en) 2012-10-01 2019-08-13 Mayo Foundation For Medical Education And Research Nanoparticle complexes of albumin, paclitaxel, and anti-VEGF antibody for treatment of cancer
US10668151B2 (en) 2012-10-01 2020-06-02 Mayo Foundation For Medical Education And Research Nanoparticle complexes of albumin, paclitaxel, and panitumumab for treatment of cancer
US11648311B2 (en) 2012-10-01 2023-05-16 Mayo Foundation For Medical Education And Research Cancer treatments
US10420839B2 (en) 2012-10-01 2019-09-24 Mayo Foundation For Medical Education And Research Methods for treating CD52-expressing cancers using compositions comprising nanoparticle complexes of paclitaxel, alemtuzumab, and albumin
US10471145B2 (en) 2012-10-01 2019-11-12 Mayo Foundation For Medical Education And Research Methods for treating cancer using nanoparticle complexes of paclitaxel, rituximab, and albumin
US10279036B2 (en) 2012-10-01 2019-05-07 Mayo Foundation For Medical Education And Research Antibody-albumin nanoparticle complexes comprising albumin, bevacizumab, and paclitaxel, and methods of making and using the same
US10279035B2 (en) 2012-10-01 2019-05-07 Mayo Foundation For Medical Education And Research Nanoparticle complexes of paclitaxel, trastuzumab, and albumin
US10413606B2 (en) 2012-10-01 2019-09-17 Mayo Foundation For Medical Education And Research Methods for treating cancer with nanoparticle complexes of albumin-bound paclitaxel and anti-VEGF antibodies
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JP2024042089A (ja) * 2016-09-06 2024-03-27 マヨ ファウンデーション フォー メディカル エデュケーション アンド リサーチ パクリタキセル－アルブミン－結合剤組成物並びに該組成物の使用及び製造方法
JP2022065061A (ja) * 2016-09-06 2022-04-26 マヨ ファウンデーション フォー メディカル エデュケーション アンド リサーチ パクリタキセル－アルブミン－結合剤組成物並びに該組成物の使用及び製造方法
US11427637B2 (en) 2016-09-06 2022-08-30 Mayo Foundation For Medical Education And Research Methods of treating PD-L1 expressing cancer
JP2019533665A (ja) * 2016-10-10 2019-11-21 アブラクシス バイオサイエンス， エルエルシー ナノ粒子製剤ならびにその作製方法および使用方法
EP3749331A4 (en) * 2018-02-06 2021-08-04 Mayo Foundation for Medical Education and Research ANTIBODY PEPTIDE COMPLEX AND THEIR USES
WO2022051414A1 (en) 2020-09-02 2022-03-10 Mayo Foundation For Medical Education And Research Antibody-nanoparticle complexes and methods for making and using the same

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