WO2001010462A1 - Treatment of patients having non-hodgkins lymphoma with bone marrow involvement with anti-cd20 antibodies - Google Patents

Treatment of patients having non-hodgkins lymphoma with bone marrow involvement with anti-cd20 antibodies Download PDF

Info

Publication number
WO2001010462A1
WO2001010462A1 PCT/US2000/040459 US0040459W WO0110462A1 WO 2001010462 A1 WO2001010462 A1 WO 2001010462A1 US 0040459 W US0040459 W US 0040459W WO 0110462 A1 WO0110462 A1 WO 0110462A1
Authority
WO
WIPO (PCT)
Prior art keywords
antibody
nhl
bone marrow
chimeric
administered
Prior art date
Application number
PCT/US2000/040459
Other languages
French (fr)
Inventor
William H. Rastetter
Original Assignee
Idec Pharmaceuticals Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Idec Pharmaceuticals Corporation filed Critical Idec Pharmaceuticals Corporation
Priority to JP2001514978A priority Critical patent/JP2003513012A/en
Priority to CA002378646A priority patent/CA2378646A1/en
Priority to AU76260/00A priority patent/AU784971B2/en
Priority to EP00965561A priority patent/EP1207906A4/en
Priority to MXPA02001398A priority patent/MXPA02001398A/en
Publication of WO2001010462A1 publication Critical patent/WO2001010462A1/en
Priority to NO20020639A priority patent/NO20020639L/en
Priority to HK03101198.5A priority patent/HK1048945A1/en

Links

Classifications

    • 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
    • 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
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered

Definitions

  • the present invention relates to a method of reducing the number of cancerous B cells in the bone marrow of a patient having a B cell lymphoma prior to radioimmunotherapy comprising administration of an anti- CD20 antibody.
  • Combined therapeutic methods of treating a patient having lymphoma with associated bone marrow involvement are also encompassed.
  • Radioimmunotherapy of B cell lymphoma is limited by marrow involvement, i.e., infiltration of the bone marrow by cancerous B lymphocytes. This complicates radioimmunotherapy in two regards: (1) antibody binding ,to diseased cells in the marrow will deliver a dose of radiation to the marrow thereby causing unwanted myelosuppression; and (2) marrow crowding of normal cells and progenitors will weaken healthy marrow reserves so that patients may actually be closer to grade 3 or 4 cytopenias than would be the case in patients without marrow involvement.
  • the patient may be less tolerant to radioimmunotherapy, e.g., with B cell depleting antibody conjugated to a radioisotope such as 90 Y or 131 I .
  • radioimmunotherapy e.g., with B cell depleting antibody conjugated to a radioisotope such as 90 Y or 131 I .
  • a radioisotope such as 90 Y or 131 I .
  • patients with greater than 25% bone marrow involvement are generally excluded from treatment with radioimmunotherapy.
  • IDEC-Y2B8 radioimmunotherapy baseline bone marrow involvement and platelet count are better predictors of hematologic toxicity than dosimetry. Blood 1998 Supplement November, 92(10): 417a (1721) Poster Board #/ Session: 393-III) .
  • the present invention relates to methods of treating patients having B cell lymphoma accompanied by bone marrow involvement comprising administering a monoclonal antibody or fragment thereof such that said bone marrow involvement is reduced or alleviated.
  • the invention encompasses methods of reducing the number of cancerous B cells in the bone marrow of a patient having non-Hodgkin' s lymphoma prior to radioimmunotherapy comprising administering to said patient an effective amount of a therapeutic antibody.
  • the methods are also useful for reducing bone marrow involvement prior to administration of antibodies labeled with cytotoxic moieties such as toxins, or any immunotherapeutic which could damage healthy bone marrow progenitors by virtue of their location in the vicinity of targeted cells which have infiltrated the bone marrow.
  • cytotoxic moieties such as toxins, or any immunotherapeutic which could damage healthy bone marrow progenitors by virtue of their location in the vicinity of targeted cells which have infiltrated the bone marrow.
  • anti-CD20 antibodies are used, although antibodies to other B cell surface markers may also be used, e.g., anti-CD19 antibodies.
  • the cell surface protein which is targeted should have the .characteristics of being expressed mainly on cancerous B cells and not generally on normal cells or B cell precursors, and preferably does not shed, internalize or modulate upon being bound by antibody.
  • antibody fragment includes any therapeutically effective portion or derivative of a therapeutic antibody, which is effective to bind to the intended target and produce the intended result . Included are Fab 2 fragments, Fab fragments, Fv fragments, domain-deleted antibodies, etc.
  • the antibodies used in the present invention are human, chimeric or humanized antibodies, such that the antibodies contain human constant region domains capable of stimulating human effector functions.
  • a preferred antibody is the chimeric anti-CD20 antibody, Rituximab ® (marketed as Rituxan ® in the U.S. and Mabthera ® in Britain) .
  • the patients who will most benefit from the present invention will be patients who have greater than 25% bone marrow involvement before being treated with the disclosed immunotherapy. Such patients may be identified by prior diagnostic imaging using antibodies radiolabeled with gamma-emitting isotopes such as X11 ln. Such patients may also be identified following bone marrow biopsy. According to a study by Wiseman et al . , such patients have a very high chance of developing thrombocytopenia due to radioimmunotherapy.
  • any patient with any level of bone marrow involvement will benefit from the present invention in that they will benefit from a decreased risk of radioimmunotherapy-induced thrombocytopenia following the disclosed treatment.
  • the dosages to be used in the present invention may vary depending on the patient, the extent of bone marrow involvement, and the antibody used.
  • Chimeric anti-CD20 antibody such as Rituximab ® may be administered at a dosage of at least about 50 mg/m 2 weekly for at least 4 weeks.
  • a preferred dosage regimen is about 375 mg/m 2 weekly for four weeks .
  • the treatment methods of the present invention naturally encompass treatment with a radiolabeled antibody subsequent to purging of the marrow.
  • the radiolabeled antibody may also be directed to any B cell surface marker which is found generally on cancerous cells and not normal cells.
  • the radiolabeled antibody is an anti-CD20 antibody.
  • Preferred radiolabels are beta emitting isotopes such as 90 Y or 131 I, but any radioisotope may be used so long as it may be effectively conjugated to the antibody, it has a relatively short decay range, and it succeeds in killing nearby cells, i.e., the cells to which it is targeted.
  • a preferred radiolabeled anti- ,CD20 antibody is Y2B8.
  • a patient should generally be treated within one week after administration of the depleting antibody, so long as they are not severely cytopenic, e.g., platelets ⁇ 150,000. If the patient is cytopenic following treatment with the depleting antibody, recovery should be allowed to occur, e.g.
  • more depleting antibody may be administered directly before immunotherapy.
  • Such a secondary dosage may be administered, for example, at about 250 mg/m 2 for about two weeks directly before or overlapping with radioimmunotherapy.
  • Radiolabeled anti-CD20 antibodies like Y2B8 are administered at a dosage of about 0.1 to 0.5 mCi/kg. It, should be clear that the treatment methods disclosed herein may be combined with other known treatment methods such as chemotherapy or radiotherapy. Bone marrow or peripheral blood stem cells may be harvested from said patient subsequent to treatment with anti-CD20 antibody and prior to treatment with said radiolabeled antibody in order to effect autologous bone marrow or stem cell transplantation after radiotherapy.
  • cytokines useful for this purpose are IL-4, GM-CSF and TNF-alpha. Cytokines may also be administered simultaneously with or prior to or subsequent to administration of the depleting antibody or radiolabeled antibody in order to stimulate immune effector functions. Cytokines useful for this purpose include interferon alpha, GM-CSF and G-CSF. Chemotherapeutic regimens may be used to supplement the therapies disclosed herein, and may be administered simultaneously with or sequentially in any order with administration of said radiolabeled antibody.
  • the chemotherapy regimen may be selected from the group consisting of CHOP, ICE, Mitozantrone, Cytarabine, DVP, ATRA, Idarubicin, hoelzer chemotherapy regime, La La chemotherapy regime, ABVD, CEOP, 2-CdA, FLAG & IDA (with or without subsequent G-CSF treatment) , VAD, M & P, C- Weekly, ABCM, MOPP and DHAP .
  • a preferred chemotherapeutic regimen is CHOP.
  • the methods of the present invention may be used to treat a variety of B cell lymphomas but are particularly useful wherein said B cell lymphoma is non-Hodgkin' s lymphoma (NHL) .
  • B cell lymphoma is non-Hodgkin' s lymphoma (NHL) .
  • Rituximab ® has already been approved for the treatment of low-grade- follicular NHL, but the present inventors have surprisingly found that Rituximab ® is also beneficial for the treatment of intermediate- and high-grade NHL, including bulky disease.
  • the lymphomas which are treatable by the methods of the present invention include low grade/ follicular non-Hodgkin' s lymphoma (NHL), small lymphocytic (SL) NHL, intermediate grade/ follicular NHL, intermediate grade diffuse NHL, chronic lymphocytic leukemia (CLL) , high grade immunoblastic NHL, high grade lymphoblastic NHL, high grade small noneleaved cell NHL, bulky disease NHL, mantle cell lymphoma, AIDS-related lymphoma and Waldenstrom' s Macroglobulinemia, so long as such lymphomas are accompanied by bone marrow involvement which complicates the availability of radioimmunotherapy.
  • NHL low grade/ follicular non-Hodgkin' s lymphoma
  • SL small lymphocytic
  • NHL intermediate grade/ follicular NHL
  • intermediate grade diffuse NHL intermediate grade diffuse NHL
  • CLL chronic lymphocytic leukemia
  • high grade immunoblastic NHL high grade lymphoblastic NHL
  • the MTD was 0.4 mCi/kg (0.3 mCi/kg for patients with mild thrombocytopenia) .
  • Adverse events were mainly hematologic, transient and reversible.

Abstract

This invention relates to methods of reducing bone marrow involvement in B cell lymphoma patients prior to radioimmunotherapy by administering monoclonal antibodies which target cancerous B cells.

Description

Treatment of Patients having Non-Hodgkins ymphoma with Bone Marrow Involvement with Anti-CD20 Antibodies
Field of the Invention
The present invention relates to a method of reducing the number of cancerous B cells in the bone marrow of a patient having a B cell lymphoma prior to radioimmunotherapy comprising administration of an anti- CD20 antibody. Combined therapeutic methods of treating a patient having lymphoma with associated bone marrow involvement are also encompassed.
Background of the Invention
Radioimmunotherapy of B cell lymphoma is limited by marrow involvement, i.e., infiltration of the bone marrow by cancerous B lymphocytes. This complicates radioimmunotherapy in two regards: (1) antibody binding ,to diseased cells in the marrow will deliver a dose of radiation to the marrow thereby causing unwanted myelosuppression; and (2) marrow crowding of normal cells and progenitors will weaken healthy marrow reserves so that patients may actually be closer to grade 3 or 4 cytopenias than would be the case in patients without marrow involvement. In either case, the patient may be less tolerant to radioimmunotherapy, e.g., with B cell depleting antibody conjugated to a radioisotope such as 90Y or 131I . As a consequence, patients with greater than 25% bone marrow involvement are generally excluded from treatment with radioimmunotherapy.
As found by Wiseman and colleagues, the clinical parameters of baseline platelet counts and degree of bone marrow involvement are accurate predictors of hematologic toxicity in patients with low-grade follicular non-Hodgkins lymphoma undergoing therapy with Y2B8, a murine anti-CD20 antibody conjugated to 90Y. For instance, eight percent of patients (2/25) without bone marrow involvement developed Grade 4 thrombocytopenia vs. 25% (1/4) of those with 0.1-5% bone marrow involvement, 45% (5/11) of those with 5-20% involvement, and 100% (6/6) with 20-25% involvement (Wiseman et al . IDEC-Y2B8 radioimmunotherapy: baseline bone marrow involvement and platelet count are better predictors of hematologic toxicity than dosimetry. Blood 1998 Supplement November, 92(10): 417a (1721) Poster Board #/ Session: 393-III) .
It would be useful to develop methods of reducing the marrow involvement in patients with non-Hodgkin' s lymphoma such that these patients may benefit from new radioimmunotherapies, thereby providing another avenue of treatment and decreasing the chance of relapse. The present invention provides such methods.
Summary of the Invention
The present invention relates to methods of treating patients having B cell lymphoma accompanied by bone marrow involvement comprising administering a monoclonal antibody or fragment thereof such that said bone marrow involvement is reduced or alleviated. Specifically, the invention encompasses methods of reducing the number of cancerous B cells in the bone marrow of a patient having non-Hodgkin' s lymphoma prior to radioimmunotherapy comprising administering to said patient an effective amount of a therapeutic antibody. The methods are also useful for reducing bone marrow involvement prior to administration of antibodies labeled with cytotoxic moieties such as toxins, or any immunotherapeutic which could damage healthy bone marrow progenitors by virtue of their location in the vicinity of targeted cells which have infiltrated the bone marrow. Preferably, anti-CD20 antibodies are used, although antibodies to other B cell surface markers may also be used, e.g., anti-CD19 antibodies. The cell surface protein which is targeted should have the .characteristics of being expressed mainly on cancerous B cells and not generally on normal cells or B cell precursors, and preferably does not shed, internalize or modulate upon being bound by antibody.
The term antibody "fragments" includes any therapeutically effective portion or derivative of a therapeutic antibody, which is effective to bind to the intended target and produce the intended result . Included are Fab2 fragments, Fab fragments, Fv fragments, domain-deleted antibodies, etc. Preferably, the antibodies used in the present invention are human, chimeric or humanized antibodies, such that the antibodies contain human constant region domains capable of stimulating human effector functions. A preferred antibody is the chimeric anti-CD20 antibody, Rituximab® (marketed as Rituxan® in the U.S. and Mabthera® in Britain) .
The patients who will most benefit from the present invention will be patients who have greater than 25% bone marrow involvement before being treated with the disclosed immunotherapy. Such patients may be identified by prior diagnostic imaging using antibodies radiolabeled with gamma-emitting isotopes such as X11ln. Such patients may also be identified following bone marrow biopsy. According to a study by Wiseman et al . , such patients have a very high chance of developing thrombocytopenia due to radioimmunotherapy. However, as the chance of developing such an adverse reaction following radioimmunotherapy increases depending on the extent of bone marrow involvement, any patient with any level of bone marrow involvement will benefit from the present invention in that they will benefit from a decreased risk of radioimmunotherapy-induced thrombocytopenia following the disclosed treatment. The dosages to be used in the present invention may vary depending on the patient, the extent of bone marrow involvement, and the antibody used. Chimeric anti-CD20 antibody such as Rituximab® may be administered at a dosage of at least about 50 mg/m2 weekly for at least 4 weeks. A preferred dosage regimen is about 375 mg/m2 weekly for four weeks .
Because the purpose of the methods of the present invention is to decrease the bone marrow involvement in patients with lymphoma preparing to undergo radioimmunotherapy, the treatment methods of the present invention naturally encompass treatment with a radiolabeled antibody subsequent to purging of the marrow.. The radiolabeled antibody may also be directed to any B cell surface marker which is found generally on cancerous cells and not normal cells. Preferably, the radiolabeled antibody is an anti-CD20 antibody.
Preferred radiolabels are beta emitting isotopes such as 90Y or 131I, but any radioisotope may be used so long as it may be effectively conjugated to the antibody, it has a relatively short decay range, and it succeeds in killing nearby cells, i.e., the cells to which it is targeted. A preferred radiolabeled anti- ,CD20 antibody is Y2B8. A patient should generally be treated within one week after administration of the depleting antibody, so long as they are not severely cytopenic, e.g., platelets <150,000. If the patient is cytopenic following treatment with the depleting antibody, recovery should be allowed to occur, e.g. nadir AGC >1000 or platelets >150,000, before radioimmunotherapy. In cases where cell recovery in the peripheral blood and/or bone marrow is permitted to occur, more depleting antibody may be administered directly before immunotherapy. Such a secondary dosage may be administered, for example, at about 250 mg/m2 for about two weeks directly before or overlapping with radioimmunotherapy.
Dosages of radiolabeled antibodies will also vary depending on the patient, the antibody specificity, half-life, stability, etc., and of course, the extent of disease. Radiolabeled anti-CD20 antibodies like Y2B8 are administered at a dosage of about 0.1 to 0.5 mCi/kg. It, should be clear that the treatment methods disclosed herein may be combined with other known treatment methods such as chemotherapy or radiotherapy. Bone marrow or peripheral blood stem cells may be harvested from said patient subsequent to treatment with anti-CD20 antibody and prior to treatment with said radiolabeled antibody in order to effect autologous bone marrow or stem cell transplantation after radiotherapy.
It may also be useful to treat patients with cytokines in order to upregulate the expression of CD20 pr other target protein on the surface of cancerous B cells prior to administration of the depleting antibody or the radiolabeled antibody. For upregulation of CD20, cytokines useful for this purpose are IL-4, GM-CSF and TNF-alpha. Cytokines may also be administered simultaneously with or prior to or subsequent to administration of the depleting antibody or radiolabeled antibody in order to stimulate immune effector functions. Cytokines useful for this purpose include interferon alpha, GM-CSF and G-CSF. Chemotherapeutic regimens may be used to supplement the therapies disclosed herein, and may be administered simultaneously with or sequentially in any order with administration of said radiolabeled antibody. The chemotherapy regimen may be selected from the group consisting of CHOP, ICE, Mitozantrone, Cytarabine, DVP, ATRA, Idarubicin, hoelzer chemotherapy regime, La La chemotherapy regime, ABVD, CEOP, 2-CdA, FLAG & IDA (with or without subsequent G-CSF treatment) , VAD, M & P, C- Weekly, ABCM, MOPP and DHAP . A preferred chemotherapeutic regimen is CHOP.
The methods of the present invention may be used to treat a variety of B cell lymphomas but are particularly useful wherein said B cell lymphoma is non-Hodgkin' s lymphoma (NHL) . Rituximab® has already been approved for the treatment of low-grade- follicular NHL, but the present inventors have surprisingly found that Rituximab® is also beneficial for the treatment of intermediate- and high-grade NHL, including bulky disease. Accordingly, the lymphomas which are treatable by the methods of the present invention include low grade/ follicular non-Hodgkin' s lymphoma (NHL), small lymphocytic (SL) NHL, intermediate grade/ follicular NHL, intermediate grade diffuse NHL, chronic lymphocytic leukemia (CLL) , high grade immunoblastic NHL, high grade lymphoblastic NHL, high grade small noneleaved cell NHL, bulky disease NHL, mantle cell lymphoma, AIDS-related lymphoma and Waldenstrom' s Macroglobulinemia, so long as such lymphomas are accompanied by bone marrow involvement which complicates the availability of radioimmunotherapy.
Exemplary treatment conditions will now be illustrated by way of the following data.
Radioimmunotherapy of Relapsed or Refractory Non-
Hodσkin's Lymphoma (NHL): Y2B8 Phase 1/ II 90Y Trial
This Phase I/II trial included 58 relapsed or refractory NHL patients, median age 60, 43% bone marrow involvement, 60% bulky lesions > 5 cm (White et al . Poster Presentation at VII International Conference on Malignant Lymphoma, Lugano, Switzerland. Annals of Oncology Suppl . 3 (1999) 10:64(215)). All patients had dosimetry by gamma camera measurements and by serial urine and blood sampling following administration of 5 mCi of 11:LIn-labeled antibody In2B8. Prior to imaging and therapy, Rituximab® was used to clear peripheral B- cells and optimize radiolabeled antibody distribution. One week later, Y2B8 (0.2, 0.3 or 0.4 mCi/kg) was administered to Group 2 & 3 patients. No bone marrow or stem cell harvest was performed.
Results :
The MTD was 0.4 mCi/kg (0.3 mCi/kg for patients with mild thrombocytopenia) . Adverse events were mainly hematologic, transient and reversible. Overall, 5 patients (10%) developed nadir platelet counts
<10,000/mm3 and 14 patients (28%) developed nadir AGC <500. Three patients (6%) acquired infections requiring hospitalization over a one year observation period. Only 2% developed HAMA/HACA. Mean serum immunoglobulins remained normal over a one year observation period. The ORR was 67% (26% CR and 41% PR) in all histologies and 82% for patients with low-grade NHL. The median TTP was 12.9+ months for responders, and the duration of response was 11.7+ months as projected by Kaplan Meier methodology. In patients with baseline splenomegaly, 4/8 (50,%) patients responded compared to 74% (29/39) without splenomegaly (p= 0.1761). Two clinical parameters, baseline platelet counts and degree of bone marrow involvement in baseline biopsy, were better at predicting severity of hematologic toxicity than dosimetry parameters.

Claims

What is Claimed:
1. A method of treating a patient having B cell lymphoma accompanied by bone marrow involvement comprising administering an anti-CD20 antibody or fragment thereof such that said bone marrow involvement is reduced or alleviated.
2. The method of claim 1, wherein said bone marrow involvement is initially greater than 25%.
3. The method of claim 2, wherein said treatment reduces said bone marrow involvement to less than 25%.
4. The method of claim 1, wherein said anti-CD20 antibody is a human, chimeric or humanized antibody.
5. The method of claim 4, wherein said anti-CD20 antibody is a chimeric anti-CD20 antibody.
6. The method of claim 5, wherein said chimeric anti-CD20 antibody is Rituximab®.
7. The method of claim 6, wherein said chimeric anti-CD20 antibody is administered at a dosage of at least about 50 mg/m2 weekly for at least 4 weeks.
8. The method of claim 7, wherein said chimeric anti-CD20 antibody is administered at a dosage of about 375 mg/m2 weekly for four weeks.
9. The method of claim 1, further comprising subsequent administration of a radiolabeled antibody.
10. The method of claim 9, wherein said radiolabeled antibody is an anti-CD20 antibody.
11. The method of claim 10, wherein said radiolabeled anti-CD20 antibody is Y2B8.
12. The method of claim 11, wherein said radiolabeled anti-CD20 antibody is administered at a dosage of about 0.1 to 0.5 mCi/kg.
13. The method of claim 9, wherein additional anti-CD20 antibody is administered simultaneously with or sequentially in either order with said radiolabeled antibody.
14. The method of claim 13, wherein at least a single dosage of said additional anti-CD20 antibody is administered as at a dosage of about 250 mg/m2.
15. The method of claim 9, wherein bone marrow or peripheral blood stem cells are harvested from said patient subsequent to treatment with anti-CD20 antibody and prior to treatment with said radiolabeled antibody.
16. The method of claim 1, wherein expression of CD20 is upregulated on the surface of cancerous B cells - 12 - prior to administration of said anti-CD20 antibody by administering at least one cytokine.
17. The method of claim 16, wherein said cytokine is selected from the group consisting of IL-4, GM-CSF and TNF-alpha.
18. The method of claim 9, further comprising treatment with a chemotherapeutic regimen simultaneously with or sequentially in any order with administration of said radiolabeled antibody.
19. The method of claim 19, wherein said chemotherapy is selected from the group consisting of CHOP, ICE, Mitozantrone, Cytarabine, DVP, ATRA, Idarubicin, hoelzer chemotherapy regime, La La chemotherapy regime, ABVD, CEOP, 2-CdA, FLAG & IDA (with or without subsequent G-CSF treatment) , VAD, M & P, C- Weekly, ABCM, MOPP and DHAP.
20. The method of claim 19, wherein the chemotherapeutic regimen is CHOP.
21. The method of claim 1, further comprising administration of at least one cytokine simultaneously with or sequentially in either order with said anti-CD20 antibody.
22. The method of claim 22, wherein said at least one cytokine is selected from the group consisting of interferon alpha, GM-CSF and G-CSF.
23. The method of claim 1, wherein said B cell lymphoma is non-Hodgkin' s lymphoma (NHL) .
24. The method of claim 23, wherein said NHL is selected from the group consisting of low grade/ follicular non-Hodgkin' s lymphoma (NHL), small lymphocytic (SL) NHL, intermediate grade/ follicular NHL, intermediate grade diffuse NHL, chronic lymphocytic leukemia (CLL) , high grade immunoblastic NHL, high grade lymphoblastic NHL, high grade small noncleaved cell NHL, bulky disease NHL, mantle cell lymphoma, AIDS-related lymphoma and Waldenstrom' s Macroglobulinemia .
25. A method of reducing the number of cancerous B cells in the bone marrow of a patient having non- Hodgkin' s lymphoma prior to radioimmunotherapy comprising administering to said patient an effective amount of anti-CD20 antibody.
26. The method of claim 25, wherein said anti-CD20 antibody is a human antibody, a chimeric antibody or a humanized antibody.
27. The method of claim 26, wherein said antibody is a chimeric antibody.
28. The method of claim 27 wherein said chimeric antibody is Rituximab®.
29. The method of claim 25, wherein said chimeric anti-CD20 antibody is administered at a dosage of at least about 50 mg/m2 weekly for at least 4 weeks.
30. The method of claim 29, wherein said chimeric anti-CD20 antibody is administered at a dosage of about 375 mg/m2 weekly for four weeks.
PCT/US2000/040459 1999-08-11 2000-07-25 Treatment of patients having non-hodgkins lymphoma with bone marrow involvement with anti-cd20 antibodies WO2001010462A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
JP2001514978A JP2003513012A (en) 1999-08-11 2000-07-25 Treatment of patients with non-Hodgkin's lymphoma with bone marrow lesions by anti-CD20 antibodies
CA002378646A CA2378646A1 (en) 1999-08-11 2000-07-25 Treatment of patients having non-hodgkins lymphoma with bone marrow involvement with anti-cd20 antibodies
AU76260/00A AU784971B2 (en) 1999-08-11 2000-07-25 Treatment of patients having non-Hodgkins lymphoma with bone marrow involvement with anti-CD20 antibodies
EP00965561A EP1207906A4 (en) 1999-08-11 2000-07-25 Treatment of patients having non-hodgkins lymphoma with bone marrow involvement with anti-cd20 antibodies
MXPA02001398A MXPA02001398A (en) 1999-08-11 2000-07-25 Treatment of patients having non-hodgkins lymphoma with bone marrow involvement with anti-cd20 antibodies.
NO20020639A NO20020639L (en) 1999-08-11 2002-02-08 Use of anti-CD20 antibody in the treatment of non-Hodgkins lymphoma involving bone marrow
HK03101198.5A HK1048945A1 (en) 1999-08-11 2003-02-18 Treatment of patients having non-hodgkins lymphoma with bone marrow involvement with anti-cd20 antibodies

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14828799P 1999-08-11 1999-08-11
US60/148,287 1999-08-11

Publications (1)

Publication Number Publication Date
WO2001010462A1 true WO2001010462A1 (en) 2001-02-15

Family

ID=22525101

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/040459 WO2001010462A1 (en) 1999-08-11 2000-07-25 Treatment of patients having non-hodgkins lymphoma with bone marrow involvement with anti-cd20 antibodies

Country Status (11)

Country Link
EP (1) EP1207906A4 (en)
JP (1) JP2003513012A (en)
CN (2) CN101259270A (en)
AU (1) AU784971B2 (en)
CA (1) CA2378646A1 (en)
HK (1) HK1048945A1 (en)
MX (1) MXPA02001398A (en)
MY (1) MY136635A (en)
NO (1) NO20020639L (en)
TW (1) TWI279233B (en)
WO (1) WO2001010462A1 (en)

Cited By (38)

* 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
EP2077281A1 (en) 2008-01-02 2009-07-08 Bergen Teknologioverforing AS Anti-CD20 antibodies or fragments thereof for the treatment of chronic fatigue syndrome
US7740847B2 (en) 2004-08-04 2010-06-22 Applied Molecular Evolution, Inc. Variant Fc regions
WO2010075249A2 (en) 2008-12-22 2010-07-01 Genentech, Inc. A method for treating rheumatoid arthritis with b-cell antagonists
WO2010074724A1 (en) * 2008-12-22 2010-07-01 Millennium Pharmaceuticals, Inc. Combination of aurora kinase inhibitors and anti-cd20 antibodies
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
US7820161B1 (en) 1999-05-07 2010-10-26 Biogen Idec, Inc. Treatment of autoimmune diseases
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
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
US8333966B2 (en) 2008-04-11 2012-12-18 Emergent Product Development Seattle, Llc CD37 immunotherapeutics and uses thereof
US8409577B2 (en) 2006-06-12 2013-04-02 Emergent Product Development Seattle, Llc Single chain multivalent binding proteins with effector function
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
US20130309244A1 (en) * 2010-12-21 2013-11-21 Duke University Methods and compositions combining immunotherapy with monocyte activation
US8653064B2 (en) 2010-02-19 2014-02-18 Millennium Pharmaceuticals, Inc. Crystalline forms of sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-D][2]benzazepin-2-yl]amino}-2-methoxybenzoate
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
US9127011B2 (en) 2009-07-31 2015-09-08 Millennium Pharmaceuticals, Inc. Pharmaceutical compositions for the treatment of cancer and other diseases or disorders
WO2016118353A1 (en) * 2015-01-23 2016-07-28 Immunomedics, Inc. Combination therapy with anti-cd74 and anti-cd20 antibodies in patients with relapsed and refractory b-cell non-hodgkin's lymphoma
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
US9724354B2 (en) 2013-03-22 2017-08-08 Millennium Pharmaceuticals, Inc. Combination of catalytic mTORC1/2 inhibitors and selective inhibitors of Aurora A kinase
US10017739B2 (en) 2012-09-06 2018-07-10 Duke University Methods of expanding and assessing B cells and using expanded B cells to treat disease
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 (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG11201901672RA (en) * 2016-09-16 2019-03-28 Nordic Nanovector Asa Treatment of non-hodgkin lymphoma using lilotomab and 177lu-lilotomab satetraxetan
CN108421048B (en) * 2016-09-28 2021-04-20 首都医科大学附属北京世纪坛医院 Nano active carbon targeted drug delivery system, preparation method and application thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5595721A (en) * 1993-09-16 1997-01-21 Coulter Pharmaceutical, Inc. Radioimmunotherapy of lymphoma using anti-CD20
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

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL141349A0 (en) * 1998-08-11 2002-03-10 Idec Pharma Corp Combination therapies for b-cell lymphomas comprising administration of anti-cd20 anti-body
US8557244B1 (en) * 1999-08-11 2013-10-15 Biogen Idec Inc. Treatment of aggressive non-Hodgkins lymphoma with anti-CD20 antibody
US6451284B1 (en) * 1999-08-11 2002-09-17 Idec Pharmaceuticals Corporation Clinical parameters for determining hematologic toxicity prior to radioimmunotheraphy

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
US5595721A (en) * 1993-09-16 1997-01-21 Coulter Pharmaceutical, Inc. Radioimmunotherapy of lymphoma using anti-CD20

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
BEHR ET AL.: "Low-versus high-dose radioimmunotherapy with humanized anti-CD22 or chimeric anti-CD20 antibodies in a broad spectrum of B cell-associated malignancies", CLIN. CAN. RES., vol. 5, October 1999 (1999-10-01), pages 3304S - 3314S, XP002935649 *
GOPAL ET AL.: "Clinical applications of anti-CD20 antibodies", J. LAB. CLIN. MED., vol. 134, no. 5, November 1999 (1999-11-01), pages 445 - 450, XP002935646 *
MALONEY ET AL.: "Newer treatments for Non-Hodgkin's lymphoma: Monoclonal antibodies", ONCOLOGY, vol. 12, no. 10, October 1998 (1998-10-01), pages 63 - 76, XP002935647 *
See also references of EP1207906A4 *
WISEMAN ET AL.: "Radioimmunotherapy of relapsed Non-Hodgkin's lymphoma with Zevalin, a Y-labled anti-CD20 monoclonal antibody", CLIN. CAN. RES., vol. 5, October 1999 (1999-10-01), pages 3281S - 3286S, XP002935648 *
WITZIG ET AL.: "Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell Non-Hodgkin's lymphoma", J. CLIN. ONCOL., vol. 17, no. 12, December 1999 (1999-12-01), pages 3793 - 3803, XP002935650 *

Cited By (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8545843B2 (en) 1999-05-07 2013-10-01 Genentech, Inc. Treatment of vasculitis
US9993550B2 (en) 1999-05-07 2018-06-12 Genentech, Inc. Treatment of pemphigus
US7820161B1 (en) 1999-05-07 2010-10-26 Biogen Idec, Inc. Treatment of autoimmune diseases
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
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
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
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
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
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
US8883980B2 (en) 2003-11-05 2014-11-11 Roche Glycart Ag 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
US10307481B2 (en) 2005-07-25 2019-06-04 Aptevo Research And Development Llc CD37 immunotherapeutics and uses thereof
EP2298815A1 (en) 2005-07-25 2011-03-23 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
US10143748B2 (en) 2005-07-25 2018-12-04 Aptevo Research And Development 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
EP2295080A2 (en) 2005-07-25 2011-03-16 Trubion Pharmaceuticals, Inc. B-cell reduction using CD37-specific and CD20-specific binding molecules
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
EP4219522A2 (en) 2007-07-09 2023-08-02 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
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
EP3597659A1 (en) 2007-07-09 2020-01-22 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP4245766A2 (en) 2007-07-09 2023-09-20 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
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
US9683047B2 (en) 2008-09-16 2017-06-20 Genentech, Inc. Methods for treating progressive multiple sclerosis
EP3095463A2 (en) 2008-09-16 2016-11-23 F. Hoffmann-La Roche AG 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
KR101741168B1 (en) 2008-12-22 2017-05-29 밀레니엄 파머슈티컬스 인코퍼레이티드 Combination of aurora kinase inhibitors and anti-cd20 antibodies
US10391100B2 (en) 2008-12-22 2019-08-27 Millennium Pharmaceuticals, Inc. Combination of aurora kinase inhibitors and anti-CD20 antibodies
WO2010074724A1 (en) * 2008-12-22 2010-07-01 Millennium Pharmaceuticals, Inc. Combination of aurora kinase inhibitors and anti-cd20 antibodies
WO2010075249A2 (en) 2008-12-22 2010-07-01 Genentech, Inc. A method for treating rheumatoid arthritis with b-cell antagonists
US9127011B2 (en) 2009-07-31 2015-09-08 Millennium Pharmaceuticals, Inc. Pharmaceutical compositions for the treatment of cancer and other diseases or disorders
US9504693B2 (en) 2009-07-31 2016-11-29 Millennium Pharmaceuticals, Inc. Pharmaceutical compositions for the treatment of cancer and other diseases or disorders
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
US9714293B2 (en) 2009-08-11 2017-07-25 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
WO2011100403A1 (en) 2010-02-10 2011-08-18 Immunogen, Inc Cd20 antibodies and uses thereof
US8653064B2 (en) 2010-02-19 2014-02-18 Millennium Pharmaceuticals, Inc. Crystalline forms of sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-D][2]benzazepin-2-yl]amino}-2-methoxybenzoate
US10017513B2 (en) 2010-02-19 2018-07-10 Millennium Pharmaceuticals, Inc. Crystalline forms of sodium 4-{[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido [5,4-D][2]benzazepin-2-YL]amino}-2-methoxybenzoate
US20130309244A1 (en) * 2010-12-21 2013-11-21 Duke University Methods and compositions combining immunotherapy with monocyte activation
US9814740B2 (en) * 2010-12-21 2017-11-14 Duke University Methods and compositions combining immunotherapy with monocyte activation
US10611999B2 (en) 2012-09-06 2020-04-07 Duke University Methods of expanding and assessing B cells and using expanded B cells to treat disease
US10017739B2 (en) 2012-09-06 2018-07-10 Duke University Methods of expanding and assessing B cells and using expanded B cells to treat disease
US9724354B2 (en) 2013-03-22 2017-08-08 Millennium Pharmaceuticals, Inc. Combination of catalytic mTORC1/2 inhibitors and selective inhibitors of Aurora A kinase
WO2016118353A1 (en) * 2015-01-23 2016-07-28 Immunomedics, Inc. Combination therapy with anti-cd74 and anti-cd20 antibodies in patients with relapsed and refractory b-cell non-hodgkin's lymphoma
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
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
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
US11584793B2 (en) 2015-06-24 2023-02-21 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
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
US11603411B2 (en) 2015-10-02 2023-03-14 Hoffmann-La Roche Inc. Bispecific anti-human CD20/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

Also Published As

Publication number Publication date
MY136635A (en) 2008-11-28
TWI279233B (en) 2007-04-21
CA2378646A1 (en) 2001-02-15
AU7626000A (en) 2001-03-05
CN100389825C (en) 2008-05-28
HK1048945A1 (en) 2003-04-25
EP1207906A4 (en) 2005-07-06
AU784971B2 (en) 2006-08-10
JP2003513012A (en) 2003-04-08
EP1207906A1 (en) 2002-05-29
MXPA02001398A (en) 2002-08-12
CN101259270A (en) 2008-09-10
CN1373671A (en) 2002-10-09
NO20020639L (en) 2002-04-11
NO20020639D0 (en) 2002-02-08

Similar Documents

Publication Publication Date Title
AU784971B2 (en) Treatment of patients having non-Hodgkins lymphoma with bone marrow involvement with anti-CD20 antibodies
US10400043B2 (en) Treatment of diffuse large-cell lymphoma with anti-CD20 antibody
JP6226216B2 (en) Combination therapy of B cell lymphoma including administration of anti-CD20 antibody
US20040213784A1 (en) Use of chimeric anti-CD20 antibody as in vitro or in vivo purging agent in patients receiving BMT or PBSC transplant
AU2017219596A1 (en) Chimeric canine anti-CD20 antibody
KR20200010472A (en) Therapeutic Paradigm for Combination Therapy with Anti-CD19 Antibody and Venetoclax
AU2005211669B2 (en) Treatment of intermediate- and high-grade non-Hodgkins lymphoma with anti-CD20 antibody
TWI280137B (en) Treatment of intermediate-and high-grade non-Hodgkins lymphoma with anti-CD20 antibody
EP2264070A1 (en) Treatment of intermediate-and high-grade non-hodgkins lymphoma with anti-CD20 antibody

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 76260/00

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2378646

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: PA/a/2002/001398

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 008116644

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 2000965561

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2000965561

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642