WO2000027428A1 - Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-cd20 antibody - Google Patents

Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-cd20 antibody Download PDF

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WO2000027428A1
WO2000027428A1 PCT/US1999/026308 US9926308W WO0027428A1 WO 2000027428 A1 WO2000027428 A1 WO 2000027428A1 US 9926308 W US9926308 W US 9926308W WO 0027428 A1 WO0027428 A1 WO 0027428A1
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antibody
patients
treatment
cll
tumor cells
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French (fr)
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Antonio J. Grillo-Lopez
Christine A. White
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Idec Pharmaceuticals Corp
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Idec Pharmaceuticals Corp
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Priority to EP99960232A priority Critical patent/EP1131093A4/en
Priority to KR1020117013133A priority patent/KR101092132B1/ko
Priority to HK02108630.7A priority patent/HK1047043B/xx
Priority to AU17149/00A priority patent/AU761844C/en
Priority to CA2350058A priority patent/CA2350058C/en
Application filed by Idec Pharmaceuticals Corp filed Critical Idec Pharmaceuticals Corp
Priority to KR1020017005716A priority patent/KR20010103655A/ko
Priority to JP2000580657A priority patent/JP4842435B2/ja
Priority to BR9915164-2A priority patent/BR9915164A/pt
Priority to MXPA01004648A priority patent/MXPA01004648A/es
Publication of WO2000027428A1 publication Critical patent/WO2000027428A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/191—Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/193—Colony stimulating factors [CSF]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2026—IL-4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A61K38/212—IFN-alpha
    • 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
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C2/00—Hot-dipping or immersion processes for applying the coating material in the molten state without affecting the shape; Apparatus therefor
    • C23C2/04—Hot-dipping or immersion processes for applying the coating material in the molten state without affecting the shape; Apparatus therefor characterised by the coating material
    • C23C2/06—Zinc or cadmium or alloys based thereon
    • C—CHEMISTRY; METALLURGY
    • C23—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; CHEMICAL SURFACE TREATMENT; DIFFUSION TREATMENT OF METALLIC MATERIAL; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL; INHIBITING CORROSION OF METALLIC MATERIAL OR INCRUSTATION IN GENERAL
    • C23C—COATING METALLIC MATERIAL; COATING MATERIAL WITH METALLIC MATERIAL; SURFACE TREATMENT OF METALLIC MATERIAL BY DIFFUSION INTO THE SURFACE, BY CHEMICAL CONVERSION OR SUBSTITUTION; COATING BY VACUUM EVAPORATION, BY SPUTTERING, BY ION IMPLANTATION OR BY CHEMICAL VAPOUR DEPOSITION, IN GENERAL
    • C23C2/00—Hot-dipping or immersion processes for applying the coating material in the molten state without affecting the shape; Apparatus therefor
    • C23C2/30—Fluxes or coverings on molten baths
    • 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
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies

Definitions

  • the present invention is directed to the treatment of hematologic malignancies associated with high numbers of circulating tumor cells by the administration of a therapeutically effective amount of a chimeric or humanized antibody that binds to the B-cell surface antigen Bp35 (CD20).
  • CD20 is a useful marker or target for B-cell lymphomas as this antigen is expressed at very high densities on the surface of malignant B-cells, i.e., those B-cells wherein unabated proliferation can lead to B-cell lymphomas.
  • CD20 or Bp35 is a B-lymphocyte-restricted differentiation antigen that is expressed during early pre-B-cell development and remains until plasma cell differentiation. It is believed that the CD20 molecule may regulate a step in the B-cell activation process which is required for cell cycle initiation and differentiation. Moreover, as noted, CD20 is expressed at very high levels on neoplastic ("tumor") B-cells.
  • ITUXAN® therapeutic anti-CD20 antibody
  • NHL low-grade non-Hodgkin's lymphoma
  • RITUXAN® radiolabeled murine anti-CD20 antibody
  • anti-CD20 antibodies and, in particular, RITUXAN® have been reported to be effective for treatment of B-cell lymphomas, such as non-Hodgkin's lymphoma, it would be beneficial if effective antibody treatments for other malignancies could be developed. More specifically, it would be beneficial if anti-CD20 antibodies could be used for treating other types of malignancies.
  • the present inventors have developed a novel treatment for hematologic malignancies characterized by a high number of tumor cells in the blood involving the administration of a therapeutically effective amount of an anti-CD20 antibody.
  • an anti-CD20 antibody will comprise a chimeric, humanized or human anti-human CD20 antibody.
  • examples of such hematologic malignancies include B-pro-lymphocytic leukemia (B-PLL) chronic-lymphocyte leukemia (CLL) and transformed non- Hodgkin's lymphoma.
  • B-PLL B-pro-lymphocytic leukemia
  • CLL chronic-lymphocyte leukemia
  • B-PLL B-prolymphocytic leukemia
  • CLL chronic lymphocytic leukemia
  • transformed non-Hodgkin's lymphoma comprising the administration of an anti-CD20 antibody.
  • B-PLL B- prolymphocytic leukemia
  • CLL chronic lymphocytic leukemia
  • the invention involves the discovery that hematologic malignancies and, in particular, those characterized by high numbers of tumor cells in the blood may be effectively treated by the administration of a therapeutic anti-CD20 antibody.
  • malignancies include, in particular, CLL, B-PLL and transformed non-Hodgkin's lymphoma.
  • Treatment of hematologic malignancy such as CLL, B-PLL and transformed non-Hodgkin's lymphoma
  • Treatment of hematologic malignancy will comprise the administration of a therapeutically effective amount of an anti-CD20 antibody, which administration may be effected alone or in conjunction with other treatment(s), e.g., chemotherapy, radiotherapy (e.g., whole body irradiation, or treatment with radiolabeled antibodies).
  • combination therapy with cytokines may be useful to upregulate CD20 on the surface of the lymphoma cells.
  • the anti-CD20 antibody will bind CD20 with high affinity, i.e., ranging from 10 "5 to 10 "9 M.
  • the anti-CD20 antibody will comprise a chimeric, primate, primatized®, human or humanized antibody.
  • the invention embraces the use of antibody fragments, e.g., Fab's, Fv's, Fab's, F(ab) 2 , and aggregates thereof.
  • a chimeric antibody is intended to refer to an antibody with non-human variable regions and human constant regions, most typically rodent variable regions and human constant regions.
  • a primatized® antibody refers to an antibody with primate variable regions, e.g., CDR's, and human constant regions.
  • primate variable regions e.g., CDR's
  • human constant regions e.g., human constant regions.
  • primate variable regions are derived from an Old World monkey.
  • a humanized antibody refers to an antibody with substantially human framework and constant regions, and non-human complementarity-determining regions (CDRs). "Substantially” refers to the fact that humanized antibodies typically retain at least several donor framework residues (of non-human parent antibody from which CDRs are derived).
  • Methods for producing chimeric, primate, primatized®, humanized and human antibodies are well known in the art. See, e.g., U.S. Patent 5,530,101, issued to Queen et al, U.S. Patent 5,225,539, issued to Winter et al, U.S. Patents
  • the selection of human constant regions may be significant to the therapeutic efficacy of the subject anti-CD20 antibody.
  • the subject anti-CD20 antibody will comprise human, gamma 1, or gamma 3 constant regions and, more preferably, human gamma 1 constant regions.
  • gamma 1 anti-CD20 antibodies as therapeutics is disclosed in U.S. Patent 5,500,362, issued to Robinson et al.
  • Methods for making human antibodies include, by way of example, production in SCID mice, and in vitro immunization.
  • a particularly preferred chimeric anti-CD20 antibody is RITUXAN®, which is a chimeric gamma 1 anti -human CD20 antibody.
  • the complete amino acid and corresponding nucleic acid sequence for this antibody may be found in U.S. Patent 5,736,137, which is incorporated by reference in its entirety.
  • This antibody which is produced in a proprietary CHO cell expression system commercialized by IDEC Pharmaceuticals Corporation, is made by a CHO cell transfectoma which was deposited on November 4, 1992, under the provisions of the Budapest Treaty at the American Type Culture Collection, located at 12301 Parklawn Drive, Rockville, MD 20852.
  • This cell line was determined to be viable and will be replaced should it become non- viable during the term of deposit.
  • This cell line was made irrevocably available upon issuance of the 5,736,137 patent and is available without restriction from the ATCC. This cell line will also be available without restriction during the lifetime of any patent that may issue based on this application.
  • the subject anti-CD20 antibody will be administered by various routes of administration, typically parenteral. This is intended to include intravenous, intramuscular, subcutaneous, rectal, vaginal, and administration with intravenous infusion being preferred.
  • the anti-CD20 antibody will be formulated for therapeutic usage by standard methods, e.g., by addition of pharmaceutically acceptable buffers, e.g., sterile saline, sterile buffered water, propylene glycol, and combinations thereof.
  • Effective dosages will depend on the specific antibody, condition of the patient, age, weight, or any other treatments, among other factors. Typically effective dosages will range from about 0.001 to about 30 mg/kg body weight, more preferably from about 0.01 to 25 mg/kg body weight, and most preferably from about 0J to about 20 mg/kg body weight.
  • Such administration may be effected by various protocols, e.g., weekly, bi-weekly, or monthly, dependent on the dosage administered and patient response.
  • cytokine administration e.g., interleukins, interferons, TNF's, colony stimulating factors, etc.
  • treatment will be effected weekly, for about 2 to 10 weeks, more typically about 4 weeks.
  • a particularly preferred dosage regimen will comprise administration of about .375 mg/kg weekly for a total of four infusions. Also, stepped-up dosing schedules may be even more preferable.
  • an yttrium-labeled anti-CD20 antibody we utilized, such as disclosed in U.S. Patent 5,736,137, incorporated by reference in its entirety herein. This antibody, 2B8-MX-DTPA, has reported efficacy in the treatment of B-cell lymphoma.
  • a particularly preferred chemotherapeutic regimen that may be used in conjunction with the subject antibody immunotherapy comprises CHOP immunotherapy, which comprises the administration of a combination of cyclophosphamide, doxorubicin, vincristine and prednisone.
  • CHOP immunotherapy comprises the administration of a combination of cyclophosphamide, doxorubicin, vincristine and prednisone.
  • Other known chemotherapeutics include methotrexate, cisplatin, toremifene and tamoxifen.
  • EXAMPLE 1 Two patients in whom we noted rapid reduction of blood tumor cells, which was associated with severe pulmonary infusion-related toxicity and thrombocytopenia, were studied. Also, two additional patients were collected from physician-submitted reports of adverse events related to RITUXAN® treatment. Pretreatment characterization of these patients included a median age of 60 years (range 26-73) with the diagnosis of B-prolymphocytic leukemia (B- PLL), chronic lymphocytic leukemia (CLL), or transformed non-Hodgkin's lymphoma. All of these patients had elevated leukocyte counts as a consequence of blood tumor involvement, bulky adenopathy and organomegaly.
  • RITUXAN® mean post-treatment Sn x 10 9 /L; range 2-120), requiring transfusion in one case. Symptoms of this syndrome required hospitalization but resolved with supportive care . Subsequent RITUXAN® treatment were well tolerated in all patients. Two subsequent patients with CLL have been treated with high blood tumor counts utilizing stepped-up dosing (100 mg day 1 followed by rest of therapy on day 1) with demonstrated efficacy, thrombocytopenia but minimal infusion-related toxicity RITUXAN® administration in patients with hematologic malignancies who have blood tumor cell involvement may be associated with a higher frequency of severe initial infusion-related reactions and thrombocytopenia mandating careful clinical monitoring. Given the preliminary activity of RITUXAN® in these patients, future studies in CLL and PLL, utilizing a stepped-up dosing schedule, is to be conducted.
  • Unlabeled immunoglobulins are attractive for the treatment of NHL as they may: mediate cytotoxicity with complement (CDC) or effector cells (ADCC); effect apoptosis; be less toxic, less immunogenic and possibly more effective than toxin- or drug-conjugated Mabs; not require the complex procedures needed for radiolabeled Mab therapy (RIT), and not produce the myelosuppression typical of high-dose RIT.
  • CDC complement
  • ADCC effector cells
  • RIT radiolabeled Mab therapy
  • US FDA 11/97; EU 6/98 Food and Drug Administration
  • ORR overall response rate
  • Median time to progression for responders was 13J months and duration of response 11.2 months.
  • N 166 patients from study 102-05, and 37 from 102-06. Abs.
  • ADCC may be an important mechanism for the clinical activity seen in
  • cytokines e.g., 11-2, G-CSF, GM-CSF, INF, are also referred to as cytokines, e.g., 11-2, G-CSF, GM-CSF, INF.
  • RITUXAN® is a monoclonal antibody targeting CD20 that has
  • LGL low-grade lymphoma
  • lymphocytic lymphoma had lower response rates (13%) than patients with
  • Hgb 11.6 g/dl (range, 7.7-14.7), platelets 75 x 107L (range, 16-160), median
  • CLL chronic lymphocytic leukemia
  • upregulation of CD20 observed on CLL cells may be limited to tumor cells
  • lymphocytic leukemia (CLL) cells may be limited to tumor cells).
  • the surface of malignant B-cells may be upregulated, thereby rendering CD20
  • the study protocol involves treating ten patients initially with GM-CSF at 250 mcg/m 2 SQ QD X 3, ten patients with
  • Antibody treatment of CLL can be combined with other conventional
  • chlorambucil leukeran
  • Chlorambucil is often combined with oral prednisone (30 to 100 mg/m 2 /d),
  • Cyclophosphamide is an alternative to chlorambucil, the usual dose being 1-2
  • Fludarabine has shown an effect in the treatment of CLL
  • anti-CD20 antibody therapy will be particularly useful for
  • Rituximab® therapy may also be combined with
  • the goals of the study are (1) to determine in fludarabine treated CLL patients

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PCT/US1999/026308 1998-11-09 1999-11-09 Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-cd20 antibody Ceased WO2000027428A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
MXPA01004648A MXPA01004648A (es) 1998-11-09 1999-11-09 Tratamientro de enfermedades hematologicas malignas asociadas con celulas tumorales de la circulacion usando el anticuerpo quimerico anti-cd20.
KR1020117013133A KR101092132B1 (ko) 1998-11-09 1999-11-09 키메라 항-ｃｄ２０항체를 이용한 순환성 종양세포와 관련된 혈액학적 악성종양의 치료법
HK02108630.7A HK1047043B (en) 1998-11-09 1999-11-09 Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-cd20 antibody
AU17149/00A AU761844C (en) 1998-11-09 1999-11-09 Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-CD20 antibody
CA2350058A CA2350058C (en) 1998-11-09 1999-11-09 Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-cd20 antibody
EP99960232A EP1131093A4 (en) 1998-11-09 1999-11-09 TREATMENT OF HEMATOLOGICAL VILTIES ASSOCIATED WITH CIRCULATING TUMOR CELLS USING CHIMERIC ANTI-CD20 ANTIBODIES
KR1020017005716A KR20010103655A (ko) 1998-11-09 1999-11-09 키메라 항-ｃｄ２０항체를 이용한 순환성 종양세포와관련된 혈액학적 악성종양의 치료법
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BR9915164-2A BR9915164A (pt) 1998-11-09 1999-11-09 Tratamento de malignidades hematológicas associadas com células de tumor circulantes usando anticorpo anti-cd20 quimérico

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Cited By (50)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004091657A2 (en) 2003-04-09 2004-10-28 Genentech, Inc. Therapy of autoimmune disease in a patient with an inadequate response to a tnf-alpha inhibitor
EP1404366A4 (en) * 2001-06-14 2006-06-07 Intermune Inc COMBINED THERAPY USING INTERFERON GAMMA AND SPECIFIC B-CELL ANTIBODIES
US7329502B2 (en) 2002-04-25 2008-02-12 The United States Of America As Represented By The Department Of Health And Human Services ZAP-70 expression as a marker for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
US7381560B2 (en) 1992-11-13 2008-06-03 Biogen Idec Inc. Expression and use of anti-CD20 antibodies
WO2008034076A3 (en) * 2006-09-15 2009-01-08 Univ Johns Hopkins Cyclophosphamide in combination with immune therapeutics
WO2008034074A3 (en) * 2006-09-15 2009-01-29 Univ Johns Hopkins Cyclosphosphamide in combination with anti-idiotypic vaccines
US7534772B2 (en) 2000-06-22 2009-05-19 University Of Iowa Research Foundation Methods for enhancing antibody-induced cell lysis and treating cancer
EP2077281A1 (en) 2008-01-02 2009-07-08 Bergen Teknologioverforing AS Anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome
US7601335B2 (en) 2005-05-20 2009-10-13 Genentech, Inc. Pretreatment of a biological sample from an autoimmune disease subject
US7682612B1 (en) 1998-11-09 2010-03-23 Biogen Idec Inc. Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-CD20 antibody
US7740847B2 (en) 2004-08-04 2010-06-22 Applied Molecular Evolution, Inc. Variant Fc regions
US7744877B2 (en) 1992-11-13 2010-06-29 Biogen Idec Inc. Expression and use of anti-CD20 Antibodies
WO2010075249A2 (en) 2008-12-22 2010-07-01 Genentech, Inc. A method for treating rheumatoid arthritis with b-cell antagonists
US7799900B2 (en) 2002-12-16 2010-09-21 Genentech, Inc. Immunoglobulin variants and uses thereof
EP2233149A1 (en) 2007-10-16 2010-09-29 ZymoGenetics, Inc. Combination of BLYS inhibition and anti-CD20 agents for treatment of autoimmune disease
US7850962B2 (en) 2004-04-20 2010-12-14 Genmab A/S Human monoclonal antibodies against CD20
EP2272868A2 (en) 2003-06-05 2011-01-12 Genentech, Inc. Combination therapy for B cell disorders
WO2011019619A1 (en) 2009-08-11 2011-02-17 Genentech, Inc. Production of proteins in glutamine-free cell culture media
EP2295080A2 (en) 2005-07-25 2011-03-16 Trubion Pharmaceuticals, Inc. B-cell reduction using CD37-specific and CD20-specific binding molecules
US7914785B2 (en) 2008-01-02 2011-03-29 Bergen Teknologieverforing As B-cell depleting agents, like anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome
EP2314318A1 (en) * 2001-01-31 2011-04-27 Biogen Idec Inc. CD80 antibody for use in combination with chemotherapeutics to treat B cell malignancies
WO2011100403A1 (en) 2010-02-10 2011-08-18 Immunogen, Inc Cd20 antibodies and uses thereof
EP2415483A1 (en) 2005-07-25 2012-02-08 Emergent Product Development Seattle, LLC Single dose use of cd20-specific binding molecules
WO2012018771A1 (en) * 2010-08-03 2012-02-09 Genentech, Inc. Chronic lymphocytic leukemia (cll) biomarkers
US8329172B2 (en) 1998-08-11 2012-12-11 Biogen Idec Combination therapies for B-cell lymphomas comprising administration of anti-CD20 antibody
US8333966B2 (en) 2008-04-11 2012-12-18 Emergent Product Development Seattle, Llc CD37 immunotherapeutics and uses thereof
WO2013004806A1 (en) 2011-07-06 2013-01-10 Morphosys Ag Therapeutic combinations of anti -cd20 and anti - gm - csf antibodies and uses thereof
US8409577B2 (en) 2006-06-12 2013-04-02 Emergent Product Development Seattle, Llc Single chain multivalent binding proteins with effector function
EP2581083A1 (en) * 2007-12-10 2013-04-17 Biocryst Pharmaceuticals, Inc. Methods of treating hematologic cancers using pnp inhibitors such as forodesine in combination with alkylating agents or anti-cd20 agents
EP2586788A1 (en) 2007-07-09 2013-05-01 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
US8529902B2 (en) 2002-10-17 2013-09-10 Genmab A/S Human monoclonal antibodies against CD20
US8557244B1 (en) 1999-08-11 2013-10-15 Biogen Idec Inc. Treatment of aggressive non-Hodgkins lymphoma with anti-CD20 antibody
CN103525823A (zh) * 2013-10-14 2014-01-22 朱慧兰 一种用于治疗荨麻疹的cd20嵌合抗体的制备方法
US8853366B2 (en) 2001-01-17 2014-10-07 Emergent Product Development Seattle, Llc Binding domain-immunoglobulin fusion proteins
US8883980B2 (en) 2003-11-05 2014-11-11 Roche Glycart Ag Antigen binding molecules with increased Fc receptor binding affinity and effector function
US9005612B2 (en) 2001-01-17 2015-04-14 Emergent Product Development Seattle, Llc Binding domain-immunoglobulin fusion proteins
US9026372B2 (en) 2007-11-21 2015-05-05 Accentia Biopharmaceuticals, Inc. Methods for providing a system of care for a high-dose oxazaphosphorine drug regimen
US9279803B2 (en) 2006-09-15 2016-03-08 The Johns Hopkins University Method of identifying patients not suitable for high-dose cyclophosphamide treatment
RU2585489C2 (ru) * 2010-04-27 2016-05-27 Рош Гликарт Аг КОМБИНИРОВАННАЯ ТЕРАПИЯ АФУКОЗИЛИРОВАННЫМ АНТИТЕЛОМ CD20 И ИНГИБИТОРОМ mTOR
US9416187B2 (en) 2003-05-09 2016-08-16 Duke University CD-20 specific antibodies and methods of employing same
EP3095463A2 (en) 2008-09-16 2016-11-23 F. Hoffmann-La Roche AG Methods for treating progressive multiple sclerosis
WO2016196344A1 (en) 2015-05-30 2016-12-08 Molecular Templates, Inc. De-immunized, shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same
EP3130349A1 (en) 2004-06-04 2017-02-15 Genentech, Inc. Method for treating multiple sclerosis
WO2017055542A1 (en) 2015-10-02 2017-04-06 F. Hoffmann-La Roche Ag Bispecific anti-human cd20/human transferrin receptor antibodies and methods of use
US9726673B2 (en) 2005-11-23 2017-08-08 Genentech, Inc. Methods and compositions related to B cell assays
US9993550B2 (en) 1999-05-07 2018-06-12 Genentech, Inc. Treatment of pemphigus
US10450379B2 (en) 2005-11-15 2019-10-22 Genetech, Inc. Method for treating joint damage
US10941205B2 (en) 2015-10-02 2021-03-09 Hoffmann-La Roche Inc. Bispecific anti-human A-beta/human transferrin receptor antibodies and methods of use
US11352426B2 (en) 2015-09-21 2022-06-07 Aptevo Research And Development Llc CD3 binding polypeptides
US11584793B2 (en) 2015-06-24 2023-02-21 Hoffmann-La Roche Inc. Anti-transferrin receptor antibodies with tailored affinity

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20090143328A1 (en) * 2001-08-13 2009-06-04 Mcdonald George Method of Treating Cancer by Administration of Topical Active Corticosteroids
US9492449B2 (en) 2008-11-13 2016-11-15 Gilead Calistoga Llc Therapies for hematologic malignancies
ES2674719T3 (es) * 2008-11-13 2018-07-03 Gilead Calistoga Llc Terapias para neoplasias hematológicas
AR078161A1 (es) 2009-09-11 2011-10-19 Hoffmann La Roche Formulaciones farmaceuticas muy concentradas de un anticuerpo anti cd20. uso de la formulacion. metodo de tratamiento.
US8822663B2 (en) 2010-08-06 2014-09-02 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
CA2821992A1 (en) 2010-10-01 2012-04-05 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
DE12722942T1 (de) 2011-03-31 2021-09-30 Modernatx, Inc. Freisetzung und formulierung von manipulierten nukleinsäuren
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
HRP20220250T1 (hr) 2011-10-03 2022-04-29 Modernatx, Inc. Modificirani nukleozidi, nukleotidi i nukleinske kiseline, te njihove uporabe
SI2791160T1 (sl) 2011-12-16 2022-07-29 Modernatx, Inc. Sestave modificirane MRNA
US10501512B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
AU2013243952A1 (en) 2012-04-02 2014-10-30 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9572897B2 (en) 2012-04-02 2017-02-21 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
WO2014081712A2 (en) * 2012-11-20 2014-05-30 Celgene Avilomics Research, Inc. Methods of treating a disease or disorder associated with bruton's tyrosine kinase
WO2014081714A2 (en) * 2012-11-20 2014-05-30 Celgene Avilomics Research, Inc. Methods of treating a disease or disorder associated with bruton's tyrosine kinase
EP2922826A4 (en) * 2012-11-20 2016-08-03 Celgene Avilomics Res Inc METHOD FOR THE TREATMENT OF A DISEASE OR DISEASE RELATED TO BRUTON TYROSINE KINASE
SMT202200337T1 (it) 2012-11-26 2022-09-14 Modernatx Inc Rna modificato al livello del terminale
EP2953457B1 (en) 2013-02-08 2020-04-08 Celgene CAR LLC Erk inhibitors and uses thereof
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
US9492471B2 (en) 2013-08-27 2016-11-15 Celgene Avilomics Research, Inc. Methods of treating a disease or disorder associated with Bruton'S Tyrosine Kinase
US10023626B2 (en) 2013-09-30 2018-07-17 Modernatx, Inc. Polynucleotides encoding immune modulating polypeptides
US10323076B2 (en) 2013-10-03 2019-06-18 Modernatx, Inc. Polynucleotides encoding low density lipoprotein receptor
CN112390883A (zh) 2013-12-17 2021-02-23 基因泰克公司 抗cd3抗体及使用方法
WO2016018665A1 (en) 2014-07-31 2016-02-04 Uab Research Foundation Apoe mimetic peptides and higher potency to clear plasma cholesterol
EP3179858B1 (en) 2014-08-13 2019-05-15 Celgene Car Llc Forms and compositions of an erk inhibitor
CR20170095A (es) 2014-09-12 2017-07-19 Genentech Inc Anticuerpos anti-cll-1 e inmunoconjugados referencias recíprocas con solicitudes relacionadas
CN107847568B (zh) 2015-06-16 2022-12-20 豪夫迈·罗氏有限公司 抗cll-1抗体和使用方法
EP3310814B1 (en) 2015-06-16 2023-08-02 F. Hoffmann-La Roche AG Humanized and affinity matured antibodies to fcrh5 and methods of use
KR20190074300A (ko) 2016-11-15 2019-06-27 제넨테크, 인크. 항-cd20/항-cd3 이중특이적 항체에 의한 치료를 위한 투약
WO2018106931A1 (en) 2016-12-07 2018-06-14 Progenity Inc. Gastrointestinal tract detection methods, devices and systems
GB201703876D0 (en) 2017-03-10 2017-04-26 Berlin-Chemie Ag Pharmaceutical combinations
CA3054632A1 (en) 2017-03-30 2018-10-04 Progenity, Inc. Treatment of a disease of the gastrointestinal tract with an immune modulatory agent released using an ingestible device
CN110831974B (zh) 2017-06-21 2024-05-14 小利兰·斯坦福大学托管委员会 针对血液恶性肿瘤的cd47靶向疗法的给药参数
CA3089287A1 (en) 2018-02-08 2019-08-15 Genentech, Inc. Bispecific antigen-binding molecules and methods of use
WO2019246312A1 (en) 2018-06-20 2019-12-26 Progenity, Inc. Treatment of a disease of the gastrointestinal tract with an immunomodulator
US12227565B2 (en) 2018-06-20 2025-02-18 Biora Therapeutics, Inc. Method of formulating a pharmaceutical composition comprising administering an immune modulator to the small intestine
CN116726361A (zh) 2018-11-19 2023-09-12 比奥拉治疗股份有限公司 用生物治疗剂治疗疾病的方法和装置
US11707610B2 (en) 2019-12-13 2023-07-25 Biora Therapeutics, Inc. Ingestible device for delivery of therapeutic agent to the gastrointestinal tract
JP7716473B2 (ja) 2020-11-04 2025-07-31 ジェネンテック， インコーポレイテッド 抗ｃｄ２０／抗ｃｄ３二重特異性抗体の皮下投薬
IL302396A (en) 2020-11-04 2023-06-01 Genentech Inc Dosage for treatment with bispecific anti-CD20/anti-CD3 antibodies
AU2022273541A1 (en) 2021-05-14 2023-11-30 Genentech, Inc. Methods for treatment of cd20-positive proliferative disorder with mosunetuzumab and polatuzumab vedotin

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5776456A (en) * 1992-11-13 1998-07-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma

Family Cites Families (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8308235D0 (en) 1983-03-25 1983-05-05 Celltech Ltd Polypeptides
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
EP0173494A3 (en) 1984-08-27 1987-11-25 The Board Of Trustees Of The Leland Stanford Junior University Chimeric receptors by dna splicing and expression
JPS63501765A (ja) 1985-11-01 1988-07-21 インタ−ナショナル、ジェネティック、エンジニアリング　インコ−ポレ−テッド 抗体遺伝子のモジュ−ル組立体、それにより産生された抗体及び用途
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US5099069A (en) 1986-09-05 1992-03-24 Gansow Otto A Backbone polysubstituted chelates for forming a metal chelate-protein conjugate
US4831175A (en) 1986-09-05 1989-05-16 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Backbone polysubstituted chelates for forming a metal chelate-protein conjugate
US5246692A (en) 1986-09-05 1993-09-21 The United States Of America As Represented By The Secretary Of Health And Human Services Backbone polysubstituted chelates for forming a metal chelate-protein conjugate
USRE38008E1 (en) 1986-10-09 2003-02-25 Neorx Corporation Methods for improved targeting of antibody, antibody fragments, hormones and other targeting agents, and conjugates thereof
US6893625B1 (en) 1986-10-27 2005-05-17 Royalty Pharma Finance Trust Chimeric antibody with specificity to human B cell surface antigen
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
CA1341235C (en) 1987-07-24 2001-05-22 Randy R. Robinson Modular assembly of antibody genes, antibodies prepared thereby and use
US4975278A (en) 1988-02-26 1990-12-04 Bristol-Myers Company Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells
US7173017B1 (en) 1987-10-28 2007-02-06 Wellstat Therapeutics Corporation Pyrimidine nucleotide precursors for treatment of systemic inflammation and inflammatory hepatitis
WO1989006692A1 (en) * 1988-01-12 1989-07-27 Genentech, Inc. Method of treating tumor cells by inhibiting growth factor receptor function
US5439665A (en) 1988-07-29 1995-08-08 Immunomedics Detection and treatment of infectious and inflammatory lesions
IL162181A (en) 1988-12-28 2006-04-10 Pdl Biopharma Inc A method of producing humanized immunoglubulin, and polynucleotides encoding the same
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5441871A (en) * 1989-06-01 1995-08-15 Health Research, Inc. Monoclonal antibody reactive to human leukemia and lymphoma cells and methods of using same for diagnosis and treatment
KR100191223B1 (ko) * 1989-07-28 1999-06-15 둘락 노먼 씨. 인터루킨-4의 정제방법 및 이를 함유하는 약제학적 조성물
US5460785A (en) 1989-08-09 1995-10-24 Rhomed Incorporated Direct labeling of antibodies and other protein with metal ions
SE8903003D0 (sv) 1989-09-12 1989-09-12 Astra Ab Novel medical use
US5124471A (en) 1990-03-26 1992-06-23 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Bifunctional dtpa-type ligand
JPH06501705A (ja) 1990-11-05 1994-02-24 ブリストル−マイアーズ　スクイブ　カンパニー 抗−腫瘍抗体及び生物学的活性剤の組合せによる相乗治療
JP3105629B2 (ja) * 1991-04-23 2000-11-06 サングスタット メディカル コーポレイション 特異的結合ペアのメンバーの細胞活性調節接合体
US5250732A (en) 1991-07-18 1993-10-05 Genentech, Inc. Ketamine analogues for treatment of thrombocytopenia
MX9204374A (es) 1991-07-25 1993-03-01 Idec Pharma Corp Anticuerpo recombinante y metodo para su produccion.
SK285960B6 (sk) 1991-07-25 2007-12-06 Biogen Idec Inc. Rekombinantné protilátky na liečenie ľudí
ZA93391B (en) * 1992-01-21 1993-10-06 Tamrock World Corp Battery changer on a mobile machine
US5686072A (en) 1992-06-17 1997-11-11 Board Of Regents, The University Of Texas Epitope-specific monoclonal antibodies and immunotoxins and uses thereof
WO1994008601A1 (en) 1992-10-14 1994-04-28 The Board Of Trustees Of The Leland Stanford Junior University Enhancement of b cell lymphoma tumor resistance using idiotype/cytokine conjugates
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
US7744877B2 (en) 1992-11-13 2010-06-29 Biogen Idec Inc. Expression and use of anti-CD20 Antibodies
US5648267A (en) 1992-11-13 1997-07-15 Idec Pharmaceuticals Corporation Impaired dominant selectable marker sequence and intronic insertion strategies for enhancement of expression of gene product and expression vector systems comprising same
US5691135A (en) 1993-01-26 1997-11-25 The Regents Of The University Of California Immunoglobulin superantigen binding to gp 120 from HIV
GB9304745D0 (en) * 1993-03-09 1993-04-28 Oncholab Ab Use of pharmaceutical formulations
US5801005A (en) 1993-03-17 1998-09-01 University Of Washington Immune reactivity to HER-2/neu protein for diagnosis of malignancies in which the HER-2/neu oncogene is associated
US5595721A (en) 1993-09-16 1997-01-21 Coulter Pharmaceutical, Inc. Radioimmunotherapy of lymphoma using anti-CD20
US5565491A (en) * 1994-01-31 1996-10-15 Bristol-Myers Squibb Company Use of phosphotyrosine phospatase inhibitors for controlling cellular proliferation
US5658590A (en) * 1995-01-11 1997-08-19 Eli Lilly And Company Treatment of attention-deficit/hyperactivity disorder
NZ305784A (en) * 1995-04-12 2001-03-30 Procter & Gamble Benzimidazole containing medicaments for treating cancers, tumors and viral infections
MX9800945A (es) * 1995-08-03 1998-04-30 Procter & Gamble Uso de griseofulvina para inhibir el crecimiento de canceres.
PL324904A1 (en) * 1995-08-04 1998-06-22 Procter & Gamble Application of fluconazole in carcinoma development inhibition
US6544787B1 (en) * 1996-11-15 2003-04-08 Hadash Medical Research Services And Development Ltd. Non-myeloablative/lymphoablative conditioning regimen to induce patient anti-donor unresponsiveness in stem cell transplantation
US6183744B1 (en) 1997-03-24 2001-02-06 Immunomedics, Inc. Immunotherapy of B-cell malignancies using anti-CD22 antibodies
US6306393B1 (en) 1997-03-24 2001-10-23 Immunomedics, Inc. Immunotherapy of B-cell malignancies using anti-CD22 antibodies
KR101063278B1 (ko) 1998-08-11 2011-09-07 바이오겐 아이덱 인크. Ｂ-세포 림프종을 치료하기 위한 항-ｃｄ２０ 항체를 포함하는 약제
AU6047099A (en) * 1998-09-24 2000-04-10 Boston Medical Center Corporation Compositions and methods for the treatment of chronic lymphocytic leukemia
AU761516B2 (en) * 1998-11-09 2003-06-05 Biogen Inc. Chimeric anti-CD20 antibody treatment of patients receiving BMT or PBSC transplants
EP1131093A4 (en) * 1998-11-09 2002-05-02 Idec Pharma Corp TREATMENT OF HEMATOLOGICAL VILTIES ASSOCIATED WITH CIRCULATING TUMOR CELLS USING CHIMERIC ANTI-CD20 ANTIBODIES
US8557244B1 (en) 1999-08-11 2013-10-15 Biogen Idec Inc. Treatment of aggressive non-Hodgkins lymphoma with anti-CD20 antibody
BR0110364A (pt) 2000-04-25 2003-12-30 Idec Pharma Corp Administração intratecal de rituximab para tratamento de linfomas do sistema nervoso central
JP2004111746A (ja) 2002-09-19 2004-04-08 Fujitsu Ltd 半導体装置及びその製造方法
KR100932340B1 (ko) 2002-10-17 2009-12-16 젠맵 에이/에스 Ｃｄ20에 대한 인간 모노클로날 항체
CN103833854B (zh) 2002-12-16 2017-12-12 健泰科生物技术公司 免疫球蛋白变体及其用途

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5776456A (en) * 1992-11-13 1998-07-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
US5843439A (en) * 1992-11-13 1998-12-01 Anderson; Darrell R. Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BLOOD, vol. 94, no. 7, 1999, pages 2217 - 2224 *
DATABASE CAPLUS, WINKLER ET AL.: "Cytokine-release syndrome in patients with B-cell chronic lymophocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab IDEC-C2B8)" *

Cited By (98)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7744877B2 (en) 1992-11-13 2010-06-29 Biogen Idec Inc. Expression and use of anti-CD20 Antibodies
US7381560B2 (en) 1992-11-13 2008-06-03 Biogen Idec Inc. Expression and use of anti-CD20 antibodies
US9296821B2 (en) 1998-08-11 2016-03-29 Biogen Inc. Combination therapies for B-cell lymphomas comprising administration of anti-CD20 antibodies
US10113000B2 (en) 1998-08-11 2018-10-30 Biogen Inc. Combination therapies for B-cell lymphomas comprising administration of anti-CD20 antibody
US8329172B2 (en) 1998-08-11 2012-12-11 Biogen Idec Combination therapies for B-cell lymphomas comprising administration of anti-CD20 antibody
EP2289543A1 (en) 1998-11-09 2011-03-02 Biogen Idec Inc. Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-cd20 antibody
US8206711B2 (en) 1998-11-09 2012-06-26 Biogen Idec Inc. Treatment of chronic lymphocytic leukemia using anti-CD20 antibodies
US7682612B1 (en) 1998-11-09 2010-03-23 Biogen Idec Inc. Treatment of hematologic malignancies associated with circulating tumor cells using chimeric anti-CD20 antibody
US9993550B2 (en) 1999-05-07 2018-06-12 Genentech, Inc. Treatment of pemphigus
US8821873B2 (en) 1999-08-11 2014-09-02 Biogen Idec Inc. Treatment of diffuse large-cell lymphoma with anti-CD20 antibody
US10400043B2 (en) 1999-08-11 2019-09-03 Biogen, Inc. Treatment of diffuse large-cell lymphoma with anti-CD20 antibody
US8557244B1 (en) 1999-08-11 2013-10-15 Biogen Idec Inc. Treatment of aggressive non-Hodgkins lymphoma with anti-CD20 antibody
US9504744B2 (en) 1999-08-11 2016-11-29 Biogen Inc. Treatment of diffuse large-cell lymphoma with anti-CD20 antibody
EP1296714B1 (en) * 2000-06-22 2009-08-26 University Of Iowa Research Foundation Combination of CpG and antibodies directed against CD19,CD20, CD22 or CD40 for the treatment or prevention of cancer.
US7534772B2 (en) 2000-06-22 2009-05-19 University Of Iowa Research Foundation Methods for enhancing antibody-induced cell lysis and treating cancer
US8853366B2 (en) 2001-01-17 2014-10-07 Emergent Product Development Seattle, Llc Binding domain-immunoglobulin fusion proteins
US9005612B2 (en) 2001-01-17 2015-04-14 Emergent Product Development Seattle, Llc Binding domain-immunoglobulin fusion proteins
EP2314318A1 (en) * 2001-01-31 2011-04-27 Biogen Idec Inc. CD80 antibody for use in combination with chemotherapeutics to treat B cell malignancies
EP1404366A4 (en) * 2001-06-14 2006-06-07 Intermune Inc COMBINED THERAPY USING INTERFERON GAMMA AND SPECIFIC B-CELL ANTIBODIES
US7981610B2 (en) 2002-04-25 2011-07-19 The United States Of America As Represented By The Department Of Health And Human Services ZAP-70 expression as a marker for chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL)
US7329502B2 (en) 2002-04-25 2008-02-12 The United States Of America As Represented By The Department Of Health And Human Services ZAP-70 expression as a marker for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
US8748114B2 (en) 2002-04-25 2014-06-10 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services ZAP-70 expression as a marker for chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL)
US8529902B2 (en) 2002-10-17 2013-09-10 Genmab A/S Human monoclonal antibodies against CD20
US7799900B2 (en) 2002-12-16 2010-09-21 Genentech, Inc. Immunoglobulin variants and uses thereof
US8562992B2 (en) 2002-12-16 2013-10-22 Genentech, Inc. Immunoglobulin variants and uses thereof
US7976838B2 (en) 2003-04-09 2011-07-12 Genentech, Inc. Therapy of autoimmune disease in a patient with an inadequate response to a TNF-α inhibitor
WO2004091657A2 (en) 2003-04-09 2004-10-28 Genentech, Inc. Therapy of autoimmune disease in a patient with an inadequate response to a tnf-alpha inhibitor
US7708994B2 (en) 2003-04-09 2010-05-04 Genentech, Inc. Therapy of autoimmune disease in a patient with an inadequate response to a TNF-α inhibitor
EP2062916A2 (en) 2003-04-09 2009-05-27 Genentech, Inc. Therapy of autoimmune disease in a patient with an inadequate response to a TNF-Alpha inhibitor
US9416187B2 (en) 2003-05-09 2016-08-16 Duke University CD-20 specific antibodies and methods of employing same
EP2272868A2 (en) 2003-06-05 2011-01-12 Genentech, Inc. Combination therapy for B cell disorders
US8883980B2 (en) 2003-11-05 2014-11-11 Roche Glycart Ag Antigen binding molecules with increased Fc receptor binding affinity and effector function
US9296820B2 (en) 2003-11-05 2016-03-29 Roche Glycart Ag Polynucleotides encoding anti-CD20 antigen binding molecules with increased Fc receptor binding affinity and effector function
US7850962B2 (en) 2004-04-20 2010-12-14 Genmab A/S Human monoclonal antibodies against CD20
EP3130349A1 (en) 2004-06-04 2017-02-15 Genentech, Inc. Method for treating multiple sclerosis
US7740847B2 (en) 2004-08-04 2010-06-22 Applied Molecular Evolution, Inc. Variant Fc regions
US7601335B2 (en) 2005-05-20 2009-10-13 Genentech, Inc. Pretreatment of a biological sample from an autoimmune disease subject
EP2298815A1 (en) 2005-07-25 2011-03-23 Trubion Pharmaceuticals, Inc. B-cell reduction using CD37-specific and CD20-specific binding molecules
EP2295080A2 (en) 2005-07-25 2011-03-16 Trubion Pharmaceuticals, Inc. B-cell reduction using CD37-specific and CD20-specific binding molecules
EP2586798A2 (en) 2005-07-25 2013-05-01 Emergent Product Development Seattle, LLC B-cell reduction using CD37-specific and CD20-specific binding molecules
EP2415483A1 (en) 2005-07-25 2012-02-08 Emergent Product Development Seattle, LLC Single dose use of cd20-specific binding molecules
US10143748B2 (en) 2005-07-25 2018-12-04 Aptevo Research And Development Llc B-cell reduction using CD37-specific and CD20-specific binding molecules
US10307481B2 (en) 2005-07-25 2019-06-04 Aptevo Research And Development Llc CD37 immunotherapeutics and uses thereof
US10450379B2 (en) 2005-11-15 2019-10-22 Genetech, Inc. Method for treating joint damage
US10654940B2 (en) 2005-11-15 2020-05-19 Genentech, Inc. Method for treating joint damage
US9726673B2 (en) 2005-11-23 2017-08-08 Genentech, Inc. Methods and compositions related to B cell assays
US8409577B2 (en) 2006-06-12 2013-04-02 Emergent Product Development Seattle, Llc Single chain multivalent binding proteins with effector function
US8673321B2 (en) 2006-09-15 2014-03-18 The Johns Hopkins University Cyclophosphamide in combination with anti-idiotypic vaccines
WO2008034076A3 (en) * 2006-09-15 2009-01-08 Univ Johns Hopkins Cyclophosphamide in combination with immune therapeutics
WO2008034074A3 (en) * 2006-09-15 2009-01-29 Univ Johns Hopkins Cyclosphosphamide in combination with anti-idiotypic vaccines
US9279803B2 (en) 2006-09-15 2016-03-08 The Johns Hopkins University Method of identifying patients not suitable for high-dose cyclophosphamide treatment
US9539267B2 (en) 2006-09-15 2017-01-10 The Johns Hopkins University Cyclophosphamide in combination with immune therapeutics
EP4245766A2 (en) 2007-07-09 2023-09-20 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP3597659A1 (en) 2007-07-09 2020-01-22 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP4219522A2 (en) 2007-07-09 2023-08-02 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP2586788A1 (en) 2007-07-09 2013-05-01 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP4335863A2 (en) 2007-07-09 2024-03-13 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP4365189A2 (en) 2007-07-09 2024-05-08 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP3327026A1 (en) 2007-07-09 2018-05-30 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP2233149A1 (en) 2007-10-16 2010-09-29 ZymoGenetics, Inc. Combination of BLYS inhibition and anti-CD20 agents for treatment of autoimmune disease
US9026372B2 (en) 2007-11-21 2015-05-05 Accentia Biopharmaceuticals, Inc. Methods for providing a system of care for a high-dose oxazaphosphorine drug regimen
US11110092B2 (en) 2007-12-10 2021-09-07 Biocryst Pharmaceuticals, Inc. Methods of treating hematologic cancers
EP2581083A1 (en) * 2007-12-10 2013-04-17 Biocryst Pharmaceuticals, Inc. Methods of treating hematologic cancers using pnp inhibitors such as forodesine in combination with alkylating agents or anti-cd20 agents
US7914785B2 (en) 2008-01-02 2011-03-29 Bergen Teknologieverforing As B-cell depleting agents, like anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome
EP2077281A1 (en) 2008-01-02 2009-07-08 Bergen Teknologioverforing AS Anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome
US9101609B2 (en) 2008-04-11 2015-08-11 Emergent Product Development Seattle, Llc CD37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof
US8333966B2 (en) 2008-04-11 2012-12-18 Emergent Product Development Seattle, Llc CD37 immunotherapeutics and uses thereof
EP4364800A2 (en) 2008-09-16 2024-05-08 F. Hoffmann-La Roche AG Methods for treating progressive multiple sclerosis
US9683047B2 (en) 2008-09-16 2017-06-20 Genentech, Inc. Methods for treating progressive multiple sclerosis
US9994642B2 (en) 2008-09-16 2018-06-12 Genentech, Inc. Methods for treating progressive multiple sclerosis
EP3747464A1 (en) 2008-09-16 2020-12-09 F. Hoffmann-La Roche AG Methods for treating progessive multiple sclerosis using an anti-cd20 antibody
EP3095463A2 (en) 2008-09-16 2016-11-23 F. Hoffmann-La Roche AG Methods for treating progressive multiple sclerosis
WO2010075249A2 (en) 2008-12-22 2010-07-01 Genentech, Inc. A method for treating rheumatoid arthritis with b-cell antagonists
US9714293B2 (en) 2009-08-11 2017-07-25 Genentech, Inc. Production of proteins in glutamine-free cell culture media
US12351641B2 (en) 2009-08-11 2025-07-08 Genentech, Inc. Production of proteins in glutamine-free cell culture media
EP3760712A1 (en) 2009-08-11 2021-01-06 F. Hoffmann-La Roche AG Production of proteins in glutamine-free cell culture media
US8512983B2 (en) 2009-08-11 2013-08-20 Martin Gawlitzek Production of proteins in glutamine-free cell culture media
WO2011019619A1 (en) 2009-08-11 2011-02-17 Genentech, Inc. Production of proteins in glutamine-free cell culture media
US10982003B2 (en) 2009-08-11 2021-04-20 Genentech, Inc. Production of proteins in glutamine-free cell culture media
US12103975B2 (en) 2009-08-11 2024-10-01 Genentech, Inc. Production of proteins in glutamine-free cell culture media
WO2011100403A1 (en) 2010-02-10 2011-08-18 Immunogen, Inc Cd20 antibodies and uses thereof
RU2585489C2 (ru) * 2010-04-27 2016-05-27 Рош Гликарт Аг КОМБИНИРОВАННАЯ ТЕРАПИЯ АФУКОЗИЛИРОВАННЫМ АНТИТЕЛОМ CD20 И ИНГИБИТОРОМ mTOR
CN103153341B (zh) * 2010-08-03 2015-05-27 霍夫曼-拉罗奇有限公司 慢性淋巴细胞性白血病(cll)生物标志物
WO2012018771A1 (en) * 2010-08-03 2012-02-09 Genentech, Inc. Chronic lymphocytic leukemia (cll) biomarkers
CN103153341A (zh) * 2010-08-03 2013-06-12 霍夫曼-拉罗奇有限公司 慢性淋巴细胞性白血病(cll)生物标志物
WO2013004806A1 (en) 2011-07-06 2013-01-10 Morphosys Ag Therapeutic combinations of anti -cd20 and anti - gm - csf antibodies and uses thereof
CN103525823A (zh) * 2013-10-14 2014-01-22 朱慧兰 一种用于治疗荨麻疹的cd20嵌合抗体的制备方法
WO2016196344A1 (en) 2015-05-30 2016-12-08 Molecular Templates, Inc. De-immunized, shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same
EP3636660A1 (en) 2015-05-30 2020-04-15 Molecular Templates, Inc. De-immunized, shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same
EP3660035A1 (en) 2015-05-30 2020-06-03 Molecular Templates, Inc. De-immunized, shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same
US11584793B2 (en) 2015-06-24 2023-02-21 Hoffmann-La Roche Inc. Anti-transferrin receptor antibodies with tailored affinity
US12252533B2 (en) 2015-06-24 2025-03-18 Hoffmann-La Roche Inc. Anti-transferrin receptor antibodies with tailored affinity
US11352426B2 (en) 2015-09-21 2022-06-07 Aptevo Research And Development Llc CD3 binding polypeptides
US11603411B2 (en) 2015-10-02 2023-03-14 Hoffmann-La Roche Inc. Bispecific anti-human CD20/human transferrin receptor antibodies and methods of use
US12030952B2 (en) 2015-10-02 2024-07-09 Hoffmann-La Roche Inc. Bispecific anti-human CD20/human transferrin receptor antibodies and methods of use
US10941205B2 (en) 2015-10-02 2021-03-09 Hoffmann-La Roche Inc. Bispecific anti-human A-beta/human transferrin receptor antibodies and methods of use
WO2017055542A1 (en) 2015-10-02 2017-04-06 F. Hoffmann-La Roche Ag Bispecific anti-human cd20/human transferrin receptor antibodies and methods of use
US12358997B1 (en) 2015-10-02 2025-07-15 Hoffmann-La Roche Inc. Bispecific anti-human A-beta/anti-human transferrin receptor antibodies

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